EP3773465A1

EP3773465A1 - Extracts of plants containing polygodial, compositions comprising such extracts and cosmetic and/or dermatological uses thereof

Info

Publication number: EP3773465A1
Application number: EP19713488.5A
Authority: EP
Inventors: Emmanuelle Gaillard; Christine PERICHET; Marina Humbert; Sophie LAVOINE; Irène Lamour
Original assignee: Robertet SA
Current assignee: Robertet SA
Priority date: 2018-04-13
Filing date: 2019-03-29
Publication date: 2021-02-17
Also published as: FR3080026A1; FR3080026B1; US20210177727A1; WO2019197173A1

Abstract

The invention relates to an extract of a plant chosen from Tasmannia lanceolata, Drimys winteri, Spilanthes acmella and Polygonum hydropiper. The invention is characterized in that the extract is able to be obtained from ground and dried leaves of said plant by supercritical CO₂ extraction at a pressure of between 120 and 350 bar and at a temperature from 35 to 60°C and in that it contains polygodial. The invention also relates to a process for obtaining such an extract. Finally, the invention relates to a composition comprising, in a physiologically acceptable medium, an effective amount of an extract of a plant chosen from Tasmannia lanceolata, Drimys winteri, Spilanthes acmella and Polygonum hydropiper, to promote wound healing and decrease inflammation in skin disorders.

Description

PLANT EXTRACTS CONTAINING POLYGODIAL, COMPOSITIONS COMPRISING SUCH EXTRACTS AND THEIR COSMETIC USES AND / OR

DERMATOLOGICAL

The present invention relates to the field of cosmetic and / or dermatological active ingredients. It relates more particularly to an extract obtained from a plant chosen from Tasmannia lanceolata, Drimys winteri, Spilanthes acmella and Polygonum hydropiper, as well as its process of obtaining, compositions comprising extracts of such plants and their cosmetic uses and / or dermatological.

Tasmannia lanceolata (also known as Drimys aromatica or Drimys lanceolata, commonly known as Tasmanian Pepper or Mountain Pepper) is a wild plant of the family Winferaceae, native of northern Tasmania.

It is a shrub with evergreen leaves. The leaves are lanceolate †, generally 4 to 8 cm long and 1 to 2 cm wide, dark green, very shiny, with a matt and clear back. The young stems are red in color. Generally speaking, the small, cream-colored, 5-petal, narrow and waxy flowers appear clustered at the end of the branches. The species is dioecious, each shrub is male or female. The female flowers are easily recognized by their ovary, a small green ball in the center of the flower. When this flower is fertilized, the fruit rounds into two lobes and blushes. It becomes black at maturity. It is necessary to have both sexes to hope a fruiting and that Tasmannia lanceolata is adorned with beautiful bunches fleshy, red to black, very decorative.

Tasmannia lanceolata is mainly used in the food industry as a substitute for pepper substitute, for example for its dried and crushed leaves and berries.

Tasmannia lanceolata, especially its roots, is also used in traditional Chinese medicine and is part of the complex formulation of compositions with many other plant extracts.

By way of example, mention may be made of document CN 1 07582791, which discloses a composition comprising in particular roots of Tasmannia lanceolata for the treatment of amenorrhea. Reference is also made to CN 107412567, which describes the use of Tasmannia lanceolata, in particular ripe fruit, in a composition for the treatment of cutaneous itches.

In addition, Garland et al. ("Sub-critical carbon dioxide extraction of hexane extract from the leaves of Tasmannia Lanceolata", The Journal of Essential Oil Research, vol.28 no.l, January 2, 2016) describes the subcritical CO2 extraction of a hexane extract of leaves of Tasmannia lanceolata, the extract containing polygodial.

JP2004083488 describes an extract of Polygonum hydroplper Linnaeus obtained by extraction in a solvent at 80 ° C for 3h with stirring, e ~ concentrated under reduced pressure at 40 ° C after filtration e † finally dried (Example 1).

JP2003073264 discloses an extract of Tasmannia lanceolata obtained by extraction of dried leaves in 10 volumes of methanol heated under reflux for 3 hours, filtration evaporation under reduced pressure and then adding distilled water to ethyl acetate to obtain extracted after separation.

KR20120031625 describes the plant Persicaria hydropiper L. Spach whose fruit is known to treat abdominal pain, edema and wounds. The fruit appears to contain 0.13% of essential oil whose main ingredients are tadeonone (polygodial), isotadeonal, confertifolin, polygonone.

US5523105 discloses a polygodial-containing plant extract by extracting a dry powder, for example from Polygonum hydroplper, Drimys lanceolata or Warburgia stublmannii, successively with petroleum ether and methanol, the extract obtained being furthermore purified by liquid chromatography. This document also discloses a plant extract containing a polygodial obtained from a dry plant by the same method using other organic solvents such as hexane, ethyl ether, acetone, ethanol and the like. methanol e † concentration under reduced pressure.

Such documents therefore do not disclose a polygodial-containing plant extract for treating skin disorders such as scars and / or stretch marks.

Moreover, to treat skin disorders such as scars and / or stretch marks, there are many topical treatments based for example on silicone, corticosteroids such as cortisone, retinoids such as tretinoin or hyaluronic acid. Occlusive treatment with a silicone dressing nevertheless requires use over several months with an occlusion of at least 12 hours per day. The main undesirable effects found are its irritation, pruritus and skin maceration.

The main adverse effects of corticosteroids at term † are: † an increase in appetite, weight gain, water retention, a tendency to aggression with insomnia and nervousness, worsening of depression, and frequently a transient imbalance of diabetes or high blood pressure.

Regarding retinoids, they are known to be photosensitive, especially isotretinoin. They are also potentially irritating, especially tretinoin.

Unlike other substances, hyaluronic acid has almost no risk of side effects. Nevertheless, allergic risks can occur. Also, the hyaluronic acid is often administered by injection.

Other active agents having an effect on skin healing, such as allantoin, zinc oxide, D-panthenol or aloe vera and hydrocotyl, are known.

There are also other relatively expensive techniques requiring the intervention of a specialist, don † peels, micro-dermabrasion, micro puncture, as well as fractional laser ablative or non-ablative treatment.

Considering the foregoing, a problem to be solved by the invention is to develop a plant extract, non-phototoxic and non-irritating to the skin, which has a healing and anti-inflammatory activity aimed at reducing, partially or totally, the irregularities from the surface of the skin without presenting the side effects of the known treatments.

The invention therefore firstly relates to an extract of a plant chosen from Tasmannia lanceolata, Drimys winteri, Spilanthes acmella and Polygonum hydropiper, characterized in that it is capable of being obtained from the ground and dried leaves of said plant. by supercritical CO2 extraction at a pressure of between 1 and 350 bar and at a temperature between 35 and 60 ° C and containing polygodial.

However, although the extracts according to the known prior art may contain polygodial, due to the specific properties of supercritical CO2, the extract obtained according to the invention has a composition different from those obtained by subcritical CO2 extraction of an extract. hexane or by the so-called methods conventional (solvent extraction, liquids or hydrodistillation), with increased quality.

In addition, a second object of the invention is a composition comprising, in a physiologically acceptable medium, an effective amount of an exfoliate obtained according to the invention for its use to promote healing and to reduce the inflammation of cutaneous disorders.

The subject of the invention is a process for obtaining an extract of a plant chosen from Tasmannia lanceolata, Drimys winteri, and Spilanthes acmella e Polygonum hydropiper, characterized in that it comprises the following stages of:

extraction of the leaves or berries, preferably leaves, from said plant with supercritical CO2 at a pressure of between 120 and 350 bars, preferably between 150 and 285 bars, and at a temperature between 35 and 60 ° C., preferably between 40 e † 50 ° C; e †

recovering said extract containing polygodial.

In this description, unless otherwise specified, it is understood that, when a given interval is given, it includes the upper and lower limits of said interval.

The invention e † the advantages that result therefrom will be better understood on reading the description e † of the non-limiting embodiments which follow, with reference to the appended drawings in which:

FIG. 1 illustrates the HPLC-DAD profile (with detection at 233 nm) of an extract of Tasmannia lanceolata according to the invention obtained according to the method of example 1;

FIG. 2 represents the anti-inflammatory activity of an extract of Tasmannia lanceolata according to the invention on fibroblasts by the translocation of NFkB;

FIG. 3 represents the healing activity of an extract of Tasmannia lanceolata according to the invention by the migration of fibroblasts;

FIG. 4 illustrates the healing activity of an extract of Tasmannia lanceolata according to the invention (photo x4 of the healed surface after 24 hours in the presence or absence of the extract);

FIG. 5 shows the effectiveness of a composition comprising an extract of Tasmannia lanceolata obtained according to the invention on the reduction of the stretch mark depth measured by the LIFEVIZ® MICRO ™ 3D Digital Dermatology Camera; FIG. 6 represents the effectiveness of a composition comprising an extract of Tasmannia lanceolata obtained according to the invention on the reduction of the stretch mark depth measured by clinical score (dermatologist);

7 represents the efficacy of a composition comprising an extract of Tasmannia lanceolata obtained according to the invention on the reduction of stretch mark staining measured by clinical score (dermatologist);

8 represents the effectiveness of a composition comprising an extract of Tasmannia lanceolata obtained according to the invention on the increase in the density of the dermis of stretch marks measured by ultrasound;

9 represents the effectiveness of a composition comprising an extract of Tasmannia lanceolata obtained according to the invention on the increase in the thickness of the dermis of stretch marks measured by ultrasound; and

- Figure 10 shows the improvement of the appearance of stretch marks by self-assessment.

The invention relates to an extract of a plant selected from Tasmannia lanceolata, Drimys w interi, Spilanthes acmella and Polygonum hydropiper.

The plant extracted preferentially chosen is Tasmannia lanceolata.

The extract according to the invention is obtained from a solid material, more particularly from the crushed and dried leaves of said plant by supercritical carbon dioxide (CO2 SC) extraction at a pressure of between 120 and 350 bar and at a temperature between 35 and 60 ° C.

Such an extract according to the invention entrusts polygodial.

Supercritical fluid extraction, and more particularly supercritical CO2, is advantageously used as an alternative to solvent extraction processes or by subcritical CO2 extraction.

CO2 in fan † supercritical fluid has significant advantages: it is neutral, non-toxic, non-polluting, non-flammable, making it a solvent called "ver †". It is also widely available at very high levels of purity and moderate costs, is easy to remove and thus has no residues in the extract. In addition, its critical parameters are low † (Te = 31 ° C, Pc = 73.8 bar).

The principle of plant extraction using CO2 SC is based on the strong variation of the CO2 solvent power as a function of the operating conditions (temperature and pressure), which makes it possible to selectively extract the molecules according to their chemical nature. Very weakly polar, CO2 is an excellent solvent for apolar or slightly polar molecules under supercritical conditions. On the basis of this principle, once the desired compound is dissolved in the SC CO2 medium, it is possible to obtain the pure extract by a simple depressurization which then causes the separation of CO2, which becomes gaseous again, e † of the extract, recovered in liquid or solid form.

This method makes it possible to avoid solvent residue removal operations (extraction, impregnation, formulation), which are essential operations when this solvent is an organic compound. In addition, the low temperatures used, below 60 ° C, can maintain the chemical integrity of the heat-sensitive molecules treated e † minimize operating costs. These properties make supercritical CO2 extraction an ecologically and economically viable alternative to distillation processes.

The extract according to the invention is preferably obtained by supercritical CO2 extraction at a pressure of between 150 and 285 bar, for example 150, 170, 200, 230, 250 or 285 bar, at a temperature of between 40 and 50 ° C, for example 40, 45 or 50 ° C.

The extraction is advantageously carried out at a rate of CO2 per loading rate in a ratio of 10 to 40 kg / kg.

The extract according to the invention is preferably obtained from the leaves or berries of the plants chosen from Tasmannia lanceolata, Drimys winteri, Spilanthes acmella and Polygonum hydropiper.

The extract according to the invention is more preferably obtained from the leaves, advantageously milled, even more advantageously finely ground.

The leaves are used fresh, semi-dry (prefaned) or dried, preferably dried under standard conditions known to those skilled in the art.

An alcoholic co-solvent, for example ethanol at a content of between 0 and 10%, may advantageously be used to obtain the extract according to the invention.

Advantageously, a fading step of the extract according to the invention thus obtained by supercritical CO2 extraction may also be subsequently performed.

By way of non-limiting illustrative examples, the bleaching may be carried out with vegetable black, by molecular distillation, or by fractionation under vacuum.

The extract obtained according to the invention may be advantageously formulated in a suitable carrier, for example a lipophilic carrier, such as miglyol, triethylcitrate, glycerine, triacetin, monoprpylene glycol, vegetable oils. For example, the extract according to the invention is formulated in 95% of lipophilic carrier. The extract according to the invention, obtained by supercritical CO2 extraction, thus contains a particularly unsaturated sesquiterpene dialdehyde of interest called polygodial (CAS 6754-20-7) of formula:

The safety of such an extract according to the invention, for example an extract of advantageously milled dried leaves of Tasmannia lanceolata, has been demonstrated through various toxicological tests.

Exfra † according to the invention es † non-photo-toxic, non-irritating to the skin e † moderately irritating to the eyes (H and CAM).

In addition, the Ames test, a biological test for determining the mutagenic potential of such an extract according to the invention has also classified the extract as non-mutagenic.

The present invention also relates to the cosmetic and / or dermatological fields, in particular that of cicatrizing and / or anti-inflammatory products.

For this purpose, another subject of the invention relates to a composition, for example a cosmetic and / or dermatological composition, comprising in a physiologically acceptable medium, an effective amount of an extract obtained according to the invention, for its use for promote healing and reduce the inflammation of skin disorders.

The extract used in the composition according to the invention, obtained from such plants, contains polygodial.

Surprisingly, the extract obtained from such plants chosen from Tasmannia lanceolata, Drimys w interi, Spilanthes acmella and Polygonum hydroplper, preferentially from Tasmannia lanceolata and more preferably from the leaves, advantageously ground and dried, from Tasmannia lanceolata, showed previously unheard-of healing and anti-inflammatory activities.

A physiologically acceptable medium refers to a medium suitable for use in contact with human animal cells, in particular epidermal cells, without toxicity, irritation, undesired allergic response, and proportionate to a benefit / benefit ratio. reasonable risk. Such a physiologically acceptable medium may comprise excipients known and used in the cosmetic and dermatological fields. Those skilled in the art will take care to choose the physiologically acceptable medium so that it does not harm the interesting properties of the extract and compositions according to the invention.

The extract used in the composition according to the invention can be obtained by any type of extraction.

By way of non-limiting example of extraction, mention may be made of techniques known to those skilled in the art, such as hydrodistillation, dry vapor entrainment, extraction with volatile solvent (s) such as hexane, methanol, ethanol alone or mixed with water, maceration, infusion, decoction, percolation, supercritical CO2 extraction.

Preferably, the extract used in the composition according to the invention is obtained according to a process comprising the following steps of:

supercritical CO2 extraction at a pressure between 120 and 350 bar, preferably between 150 and 285 bar, and at a temperature between 35 and 60 ° C, preferably between 40 and 50 ° C; and

recovering said extract containing polygodial.

The extract preferably used in the composition according to the invention comprises a polygodial concentration of between 0.1% and 10%, preferably between 0.2% and 5%, more preferably between 0.5% and 3% by weight of the total weight of the extract, for example 0.5%, 1%, 1, 5%, 2%, 2.5% or 3%.

The extract used in the composition according to the invention is preferably obtained from the leaves or berries of such plants chosen from Tasmannia lanceolata, Drimys winteri, Spilanthes acmella and Polygonum hydropiper, more preferably leaves, advantageously ground, even more advantageously finely. crushed.

The extract used in the composition according to the invention can be obtained from fresh, semi-dry (prefaned) or dried leaves, preferably from dried leaves under standard conditions known to those skilled in the art.

The composition used according to the invention comprises such an extract of a plant chosen from Tasmannia lanceolata, Drimys winteri, Spilanthes acmella and Polygonum hydropiper at a concentration of between 0.01 and 20% by weight of the total weight of the composition, preferably between 0.1% and 10%, for example 1%, 2%, 5% and 10%. The composition used according to the invention is formulated to be administered orally or to be applied fopically to the skin.

The skin refers to an organ composed of several layers of tissue, which plays the role of protective envelope of the body. It provides a physical barrier that protects the underlying organs and tissues from physical, chemical, and external biological aggression. On an anatomical level, the skin consists of two main parts. The thin superficial part, the epidermis, attached to a thicker internal part: the dermis. A third layer, deeper, is the hypodermis but is not classically not assimilated to a layer of skin. The entire skin of the integuments (nails, hair, hair) constitutes the integument.

The skin may also refer to the scalp.

The skin does not therefore designate the underlying tissues in continuity with the skin such as the mucous membranes.

The composition used according to the invention is therefore not intended to be applied to the mucous membranes.

The composition used according to the invention may be formulated in a form suitable for oral administration, for example as a dietary supplement.

The oral dosage forms used may be solid or liquid. Solid oral forms are generally tablets, hard capsules (capsules), soft capsules, sachets comprising a powder or granules. Liquid oral forms are generally oral solutions, syrups, elixirs, oral emulsions, oral suspensions, drinkable drops.

Preferably, the oral composition used according to the invention is in the form of a soft capsule.

The composition used according to the invention may be in various forms acceptable for topical application, especially in solid form or in liquid form, depending on the physiologically acceptable medium used.

The topical composition may be in the form of a water-in-oil (W / O) or oil-in-water (O / W) emulsion, suspension, oil, gel, paste, cream, lotion, solution, serum, for example an aqueous, alcoholic, hydroalcoholic or fatty solution, powder.

Preferably, the topical composition according to the invention is in the form of oil, cream, gel, serum. The composition according to the invention comprising an effective amount of an exfoliate of a plant selected from Tasmannia lanceolata, Drimys winteri, Spilanthes acmella and Polygonum hydropiper is used to promote healing and reduce inflammation of skin disorders.

Skin disorders are understood to mean the alterations or irregularities of the surface of the skin, which may result from physiological problems that have been solved or not, or may be caused by physical or chemical treatments.

The alterations or disorders of the skin surface, including irregularities of the skin, are for example chosen from those associated with acne skin, signs of skin aging, weight gain and weight loss. , or to a pregnancy. They may also be caused by physical or chemical treatments, whether cosmetic treatments or pharmaceutical treatments, or caused by skin conditions, which alterations or irregularities of the skin remain after said disorders are physiologically resolved.

The healing process of the skin brings together several distinct phases.

The initial phase is accompanied by a strong vascular vasoconstrictor response followed by an increase in capillary permeability and vasodilatation. Thrombin and extravascular collagen contribute to the aggregation and activation of platelets in the clot. Many proteins are delivered by the influx of blood at the site of the injury, which allows the formation of the fibrin clot. The fibrin-fibronectin network provides a reservoir for the many growth factors released in the wound (PDGF, bFGF, TGFα, | 3) that are responsible for the activation of neutrophils and macrophages. These cells will then fight against the infection, clean the wound and participate in local renutrition.

Then, the inflammatory phase is accompanied by vasodilation leading to redness and sensation of heat and pain. Neutrophils and monocytes are attracted to the wound not only by factors released by platelets, but also by bacterial peptides, complement factors, and fibrin degradation products. The neutrophils are the first leukocytes present in the wound; they release proteolytic enzymes such as elastase e † collagenases e † provide local anti-infectious function. Monocytes bind to endothelial cells and migrate into the wound. Once in the tissue environment, they differentiate into macrophages and adhere to extracellular matrix proteins; but they are especially, like platelets, a source of cytokines such as IGF, TGF, TNF or PDGF. These substances amplify the inflammatory response and stimulate the proliferation of fibroblasts, the production of collagen and more broadly, the proliferation of granulation tissue.

This phase corresponds to the transition between inflammation and scarring by secreting growth factors that stimulate cell proliferation and matrix tissue formation.

The tissue repair phase then takes place with formation of the granulation tissue. This phase lasts 10 to 15 days and corresponds to the proliferation of fibroblasts, to angiogenesis and to the synthesis of the extracellular matrix. This phase is largely dependent on cytokines (IGF1, EGF, TNFα, TGFβ, PDGF-BB) that promote the migration and proliferation of fibroblasts. Fibroblasts synthesize a new extracellular matrix consisting mainly of early collagen type III, fibronectin, proteoglycans (hyaluronic acid, chondroitin sulfate ...). They also participate in matrix remodeling by producing proteolytic enzymes including metalloproteinases. The matrix also serves as a reservoir of growth factors.

This is followed by re-epithelialization, which takes place in several phases: migration of epithelial cells from the banks or appendages, their multiplication and differentiation of the reformed epidermis.

Keratinocytes migrate to the matrix components and re-epithelialize the wound. Once the wound is closed by a monolayer of keratinocytes, they stop their migration, multiply and differentiate.

The final phase of healing of the skin corresponds to the maturation of the scar with a re-modeling of the tissues by the reorganization of the neosynthesized collagen fibers which will eventually reform a healthy tissue. Remodeling of the extracellular matrix passes through an inflammatory and proliferative phase lasting up to two months after closure of the wound. Little by little the granulation tissue becomes scarce into fibroblasts, a denser collagenous structure appears, while the vascular network is organized. Matrix remodeling will increase the resistance of the scar considerably up to 80-90% of its initial strength by the sixth week. Fibronectin and hyaluronic acid are gradually being replaced by collagens, elastic fibers and glycosaminoglycans (GAGs). Age, tension forces, pressure influence the synthesis and organization of collagen molecules. The scars are nevertheless, in all cases, less resistant and less elastic than the normal skin, partly because of a certain elastin deficiency.

The composition of the extracellular matrix plays an important role in the migration of inflammatory cells, in the differentiation of conjunctive cells and epithelial cells. The healing process is characterized by important modifications of the extracellular matrix.

During healing, the extracellular matrix contains GAGs, fibronectin and type III collagen.

The end of the healing process is characterized by:

a progressive decrease in the concentration of fibronectin;

a modification of the GAG composition of the extracellular matrix;

- a deterioration of type III collagen, replaced by type I collagen.

Fibronectin stimulates the migration of endothelial cells and fibroblasts into the inflammatory focus.

The composition according to the invention is preferably used to prevent and / or promote the reduction of scars.

The composition according to the invention is also preferably used to prevent and / or promote the reduction of stretch marks.

The stretch marks are presented as parallel linear or spindle streaks of 1 or more cm in length and 1 mm to 1 cm in width. They are depressed and covered with a wrinkled epidermis of pearly white (in case of old stretch mark) or pink or purple (in case of recent stretch mark). They are almost always multiple and symmetrical and their direction is generally radiated on the breasts, vertical and oblique on the flanks, transverse on the lumbosacral region.

The stretch mark formation mechanism was initially perceived as solely the result of the rupture of the elastic tissue after a large mechanical tension. In fact, stretch marks seem to result first and foremost from fibroblast involvement. It was highlighted at the level of stretch marks overexpression of interferon gamma at the expense of TGF-6 thus preventing proper functioning of the fibroblast and healing of good quality. The consequences are degeneration of collagen (stretched and atrophic collagen bundles) and elastic fibers (Thick and tortuous on the periphery of the stretch marks and decrease of the superficial network) responsible for a decrease in the thickness of the dermis.

The composition according to the invention is more preferably used to reduce the depth and color of stretch marks as well as to increase the density and thickness of the dermis of stretch marks.

The invention is illustrated hereinafter, without any limiting character, by an exemplary embodiment, examples of formulations of a composition containing a Tasmannia lanceolata extract obtained according to the invention and the results of biological activities. .

Example 1 Process for Obtaining a Tasmannia lanceolata Extract by Supercritical CO2 Extraction

According to an exemplary preferred embodiment of the invention, the extract is obtained from leaves of Tasmannia lanceolata. 250 kg of ground dried leaves are extracted with supercritical CO2 at a pressure of 290 bars and a temperature of 45 ° C. with a co-solvent ratio of ethanol of 4%. The extract obtained is then concentrated and diluted in miglyol (25% extract / 75% miglyol): 77 kg of extract 25% on miglyol are obtained. This extract is then decolorized with 3% of activated carbon: 77 kg of extract are thus diluted with ethanol (385 kg) to which 3% of activated charcoal is added 2.31 kg. This discoloration is carried out with stirring. Then filtration is done, and the filtrate is concentrated.

The extract thus obtained is finally diluted on a support type miglyol to standardize the ingredient to 0.5% polygodial.

The analytical composition of the extract obtained according to Example 1 was determined by HPLC-DAD (with detection at 233 nm), † illustrated by the chromafogram of FIG. 1 under the operating conditions described below. .

HPLC-DAD operating conditions:

Agilent Poroshell Column 120 S-C 18, 4.6 x 150 mm, 2.7 meters

Column temperature: 30 ° C

Flow rate: 1 ml / min

As illustrated by the chromafogram of FIG. 1, the Polygodial content of 0.53% by weight of the total weight of the extract.

The exfray † preferably used in the composition according to the invention comprises a polygodial concentration of between 0.1% and 10%, preferably between 0.2% and 5%, more preferably between 0.5% and 3%. by weight of the total weight of the extract, for example 0.5%, 1%, 1, 5%, 2%, 2.5% or 3%.

Example 2: Dry oil

Prepare phase A: mix until mixture is uniform. Example 3: Veraetures cream for the body

Prepare phase A † G homogenize.

Prepare phase B and add to aqueous phase A. Homogenize until uniform.

Melt the Cl phase at 45 ° C, once liquid add to phase C and mix until it is uniform.

Add C + Cl to A + B. Homogenize until it is uniform.

Add phase D to the formula

Adjust the formulation to pH 5.0 - 6.0 with citric acid (50% Aq.) Example 4: acne healing cream

Prepare phase A e G homogenize

Prepare phase B, add it to aqueous phase A. Homogenize until it is uniform.

Prepare C and mix until a homogeneous mixture

Add C to A + B. Homogenize until this self

Add phase D to the formula

Adjust the formulation to pH 5.0 - 6.0 with citric acid (50% Aq.) Example 5: soft capsule

Example 6: soft capsule

Example 7 Demonstration of the Anti-inflammatory Activity by the Translocation of NFkB

To evaluate the properties of an extract of Tasmannia lanceolata according to the invention to modulate an induced inflammation, the cells were pre-exposed to the extract of Tasmannia lanceolata obtained according to Example 1 at 5% in miglyol or in SN50 peptide (a reference inhibitor of NFkB translocation) prior to LPS exposure. 24 hours after the deposition of the cells, the fibroblasts were exposed to 5 concentrations of extracts of Tasmannia lanceolata or at a concentration of the SN50 peptide for 24 hours. Then, the cells were exposed for 3 and 24 hours to LPS extracts (1 ng / mL) and Tasmannia lanceolata extract or SN50 peptide. Finally, after 3 hours of exposure, cells were fixed and stained for quantification of NFkB.

The results obtained are shown in Table 1 below and more particularly illustrated in FIG. 2. It appears that the extract of Tasmannia lanceolata according to the invention induces a significant decrease in the translocation of NFkB compared to the control with LPS ( CTRL-), especially for these concentrations below 50 ppm.

The extract of Tasmannia lanceolata according to the invention thus reduces the inflammation of the skin.

Table 1:

LPS at 1 ng / mL induces moderate inflammation, characterized by a significant translocation of NFkB for 10% of the cell population compared to control alone.

The SN50 peptide (CTRL +) significantly inhibits the translocation of NFKB induced bet ng / mL of LPS after 3 hours of exposure.

Tasmannia lanceolata extract at 1, 2.5, 5 and 10 ppm shows no cytotoxicity and induces a significant decrease of approximately 50% for the 2.5, 5 and 10 ppm NFkB in human fibroblasts.

EXAMPLE 8 Demonstration of Healing Activity by Fibroblast Migration

The cells were pre-treated with the extract of Tasmannia lanceolata obtained according to Example 1 at 5% in miglyol and Nucblue (live cell assay nuclei dye) in growth medium without growth factor. After 24 hours of pre-treatment, the cells were mechanically scratched and the medium renewed. Images have been taken with x4 magnification for 24 hours.

The calculations were made as follows:

D = healed surface = Surface TOH Surface T2 H where the Surface at T0 is the initial surface after scratching and the Surface T24H is the same surface measured after 24h; and D treatment

% of healed area compared to mean CTRL x 100 (D CTRL without growth factors) where the treatment corresponds to the receiving well either Tasmannia lanceolata extract at a given concentration or medium containing growth factors as a positive control.

The results obtained are shown in Table 2 below. A statistical comparison was made between the control without growth factor and the Tasmannia lanceolata extract using a T-test.

Table 2:

As illustrated by FIGS. 3 and 4, the Tasmanian pepper extract according to the invention induces a significant increase (+ 65% after 24 hours) of fibroblast migration compared to control (without growth factor) and this for concentrations of only 1 to 2.5 ppm.

EXAMPLE 9 Ex-Nino Test of the Activity of the Tasmannia lanceolata Extract on Skin Fragments Containing Borders by Measurement of TGF-β, Pro-Collaaene I and Elastin

Skin fragments with stretch marks of 5 different donors were deposited in inserts themselves positioned on culture wells. Culture medium (antibiotics, FCS) was added to the bottom of the wells, a passage being carried out by slow diffusion between the two compartments through a porous membrane (12 miti). The skin fragments were kept alive for 1 2 days at 37 ° C and in air / CC 2 atmosphere. The skins were treated daily with the extract of Tasmannia lanceolata according to the invention obtained according to Example 1 at 5% in miglyol topically (15 ml / cm ² ).

A comparison was made between the 2 following conditions:

- skin with stretch marks (witness)

skin with stretch mark + extract of Tasmannia lanceolata according to the invention at 2%.

Dosage of TGF-b:

TGF-b, synthesized in particular by keratinocytes, is a stimulation factor for the dermal fibroblast that will synthesize collagen I and III. The TGF-b assay was performed by an immunoassay technique with spectrophotometric concentration reading (μg / ml) (BioTechne assay kits). The skin fragments having the same surface (checking the weight of each fragment), the assay was carried out from the culture supernatants.

The results obtained (concentration of TGF-β in μg / ml) are shown in Table 3 below:

Table 3:

* statistical comparison with the control group

A composition comprising an extract of Tasmannia lanceolata according to the invention induces a significant increase, on average more than twice, in the concentration of TGF-B in the treated skin compared to the control.

Dosage of pro-collaaene I:

The collected skin fragments were solubilized in tris-HCl buffer, 100 mM, 100 mM NaCl, Triton XI, 000.1%, pH 7.4. After grinding with a poffer, the amount of pro-collagen type I (pg / ml) was evaluated by ELISA (Human Pro-Collagen I alpha 1, BioTechne).

The results obtained (concentration of pro-collagen I in pg / ml) are listed in Table 4 below: Table 4:

* statistical comparison with the control group

A composition comprising an extract of Tasmannia lanceolata according to the invention induces a significant increase, on average of at least 30%, in the concentration of pro-collagen 1 in the treated skin compared to the control. Biochemical determination of G elastin:

Insoluble elastin extracted biopsies with 0.25M oxalic acid at 100 ° C as soluble fragments of alpha elastin polypeptides.

After centrifugation to remove undigested tissues, the amount of soluble elastin was measured by a spectrocolorimetric assay method at 513 nm, after fixation of the dye 5,10,15,20- † e-raphenyl-21,23-porphirine Tetrasulfonate (Fastin Elastin Assay Kit, Interchim).

The results obtained (elastin concentration in mg / mg) are listed in Table 5 below:

Table 5:

* Statistical comparison with the control group A composition comprising an extract of Tasmannia lanceolata according to the invention induces a significant increase, on average of more than 10%, in the concentration of elastin in the treated skin compared to the control.

According to the results thus obtained, a composition according to the invention comprising an extract of Tasmannia lanceolata promotes the healing of the skin and thus the reduction of scars and vertigo.

Example 10: Clinical study against placebo to prove the effectiveness of a composition comprising an extract of Tasmannia lanceolata according to the invention against vergefures

The study was conducted on 30 women, with an average age of 47.7 years.

15 women received the composition comprising an exfray of Tasmannia lanceolata according to the following invention: Table 6: TASMANOL ™ Oil According to the Invention

15 other women received the following placebo composition; a woman is out of study for reasons unrelated to the study.

Table 7: Placebo

Each composition was respectively applied twice daily in areas with stretch marks (thighs, hips, belly) for a period of two months.

The depth and color of the stretch marks have been evaluated.

Measurements of the density and thickness of the dermis of stretch marks have also been made.

Finally, a self-evaluation of these same criteria was carried out by the subjects.

The results obtained are as follows.

As illustrated by FIGS. 5 and 6, after 8 weeks of daily application, the composition according to the invention tested induces a significant reduction (p <0.05) in the stretch mark depth measured by the 3D digital dermatology camera. LIFEVIZ® MICRO ™ as well as clinical score (p <0.01) between 0 and 3 with:

0 = shallow stretch marks - smooth skin; 1 = slightly deep stretch marks - almost smooth skin;

2 = moderately deep stretch marks - rough skin; and

3 = deep stretch marks - very rough skin).

A reduction in the depth of the stretch marks was observed in 80% of the subjects with the composition according to the invention tested.

As illustrated by FIG. 7, after 8 weeks of daily applications, the composition according to the invention tested induces a significant reduction (p <0.01) in stretch mark staining measured by clinical score between 0 and 3 with:

0. = little colored stretch marks;

1 = slightly colored stretch marks;

2 = moderately colored stretch marks; and

3 = colored stretch marks

A reduction in the color of the stretch marks was observed in 66.7% of the subjects with the composition according to the invention tested.

As shown in FIG. 8, the composition according to the invention tested induces a significant increase in the density of the dermis of stretch marks after 4 weeks of treatment (p <0.05) and after 8 weeks of treatment (p <0, 01) measured by ultrasound.

An increase in the density of the dermis at the level of stretch marks was observed in 87% of the subjects with the composition according to the invention tested.

As illustrated by Figure 9, the composition according to the invention tested induced a significant increase in the thickness of the dermis of stretch marks after 8 weeks of treatment (p <0.01) measured by ultrasound (miti).

An increase in the thickness of the dermis at the level of stretch marks was observed in 87% of the subjects with the composition according to the invention tested.

As shown in Figure 10, after 8 weeks of daily application, subjects reported a marked improvement in the appearance of stretch marks:

- Stretch marks are less visible † for 80% of subjects;

- the stretch marks are † less deep for 80% of the subjects;

- the skin is softer for 93% of subjects;

- the skin is smoother for 80% of subjects.

According to the results thus obtained, a composition comprising an extract of Tasmannia Lanceolata obtained according to the invention reduces the appearance and coloring of stretch marks, reduces the depth of stretch marks, increases the density of the dermis and improves the softness of the skin.

Claims

1. Extract of a plant selected from Tasmannia lanceolata, Drimys winteri, Spilanthes acmella and Polygonum hydropiper, characterized in that it is obtainable from the crushed and dried leaves of said plant by supercritical CO2 extraction at a pressure of between 1 and 350 bar and at a temperature between 35 and 60 ° C and in that they entrust polygodial.

2. Extract according to claim 1, characterized in that it is capable of being obtained by supercritical CO2 extraction at a pressure between 150 and 285 bar and at a temperature between 40 and 50 ° C.

3. Extract according to one of claims 1 or 2, characterized in that it is obtainable from the ground and dried leaves of Tasmannia lanceolata.

4. Composition comprising in a physiologically acceptable medium, an effective amount of an extract according to one of claims 1 to 3 for its use to promote healing and reduce inflammation of skin disorders.

5. Composition for use according to one of claims 4 to 7, characterized in that it comprises the extract at a concentration between 0.01% and 20% by weight of the total weight of the composition.

6. Composition for use according to claim 5, characterized in that it comprises the extract at a concentration of between 0, 1% and 10% by weight of the total weight of the composition.

7. Composition for use according to one of claims 4 to 6, characterized in that it is in the form of oil, cream, gel, serum to be applied topically to the skin.

8. Composition for its use according to one of claims 4 to 6, characterized in that it is in a form suitable for oral administration fan † as a dietary supplement.

9. Composition according to one of claims 4 to 8 for its use to prevent and / or promote the reduction of scars.

10. Composition according to one of claims 4 to 8 for its use to prevent and / or promote the reduction of vergefures.

1 1. The composition of claim 10 for reducing the depth and color of vergefures and for increasing the density and thickness of the dermis of vergefures.

12. Process for obtaining an exfrai † of a plant chosen from Tasmannia lanceolata, Drimys winteri, and Spilanthes acmella e † Polygonum hydropiper, characterized in that it comprises the following stages of:

extracting the leaves or berries of said plant with supercritical CO2 at a pressure of between 120 ° C. and 350 ° C. and at a temperature between 35 ° and 60 ° C .; e †

recovering said extract containing polygodial.

13. The method of claim 12, characterized in that it comprises the following steps of:

extracting the sheets of said plant with supercritical CO2 at a pressure of between 150 ° C. and 285 bar and at a temperature of between 40 ° C. and 50 ° C .; e †

recovering said extract containing polygodial.

14. The method of claim 12 or 13, characterized in that the leaves of said plant are crushed and dried before their extraction.

15. Method according to one of claims 12 to 14, characterized in that said plant is † Tasmannia lanceolata.