WO2014180808A1

WO2014180808A1 - Use of petroselinic acid for combating aesthetic disorders of the figure associated with adipose tissue modifications

Info

Publication number: WO2014180808A1
Application number: PCT/EP2014/059162
Authority: WO
Inventors: Audrey Gueniche; Yann Mahe; Carole BRU
Original assignee: L'oreal
Priority date: 2013-05-07
Filing date: 2014-05-06
Publication date: 2014-11-13
Also published as: FR3005408B1; FR3005408A1

Abstract

The present invention relates to the use of petroselinic acid for combating aesthetic disorders of the figure associated with adipose tissue modifications.

Description

The present invention relates to the use of petroselinic acid or of combinations comprising at least petroselinic acid, of use for improving and/or slimming down the figure and improving the quality of adipose tissue. The quality of adipose tissue is in particular impaired by the presence of cellulite or of the orange peel syndrome or else is affected when there is a change, in particular an abrupt change, in a person's weight, upwards or downwards.

Human skin consists of three compartments, namely a superficial compartment, which is the epidermis, the dermis and a deep compartment, which is the hypodermis. The latter compartment essentially consists of a type of cells that are specialized in the accumulation and storage of fats, the adipocytes.

The extracellular matrix (ECM) of human skin consists of various macro molecules responsible for the mechanical strength of the skin, for its suppleness and for its elasticity, and also for the important physiological functions (moisturization, thermoregulation and regulation of skin permeability).

The macromolecules of the ECM have been arbitrarily classified into four families. The first two consist of fibrous and structural macromolecules, collagens and elastin, whereas the other 2 are glycoconjugates (glycoproteins and proteoglycans). Collagens represent 70% of the ECM proteins. The ECM is made up of numerous types of collagen. Thus, type IV collagen is specific to the basal membrane, type VI and VII collagens (microfibrillar collagens) are found in the dermal-epidermal junction, and type XII, XIII and XIV collagens are found in the deep dermis. The firmness and the pressure resistance of the skin depend in particular on the collagen fibres of the basal membrane and of the dermal-epidermal junction. With age, it has been described that the type I collagen/type III collagen ratio appears to increase.

Several types of collagen can be distinguished:

- interstitial collagens (type I, II, III) of fibrillar structure, which are responsible for the cohesion, rigidity and mechanical strength produced essentially by the fibroblasts;

- basal lamina collagens (type IV) synthesised by the adjacent cells and in the skin by the keratinocytes. In addition to their mechanical role, some of these domains may act on cell metabolism; - non- fibrillar type V and XIII collagens which are not found in the skin.

Collagens constitute a three-dimensional framework to which fibronectins anchor themselves.

It is the collagen fibres which give the dermis solidity. Collagen fibres consist of fibrils sealed to one another, thus forming more than 10 types of different structures. The solidity of the dermis is in large part due to the entanglement of the collagen fibres packed together in all directions. The collagen fibres contribute to the elasticity and to the tonicity of the skin and/or the mucous membranes.

The collagen fibres are constantly renewed, but this renewal decreases with age, which leads to thinning of the dermis. This thinning of the dermis is also due to pathological causes, for instance hypersecretion of corticoid hormones, certain pathological conditions, or else vitamin deficiencies. It is also accepted that extrinsic factors such as ultraviolet radiation, smoking or certain treatments (glucocorticoids, vitamin D and derivatives, for example) also have an effect on the skin and its collagen content.

Various factors lead to collagen degradation, with all the consequences that can be envisaged on the structure and/or the firmness of the skin and/or the mucous membranes. Although they are very strong, collagen fibres are sensitive to certain enzymes known as collagenases. Collagen fibre degradation leads to the appearance of flaccid and wrinkled skin which human beings, preferring the appearance of smooth and taut skin, have always sought to combat.

Collagenases are part of a family of enzymes known as metalloproteinases which are themselves members of a family of proteolytic enzymes (endoproteases or endopeptidases). These enzymes are weakly expressed in normal physiological situations such as organ growth and tissue renewal. Their overexpression in humans and their activation are associated with numerous processes, which are occasionally pathological, involving the destruction and remodelling of the matrix. This either causes uncontrolled resorption of the extracellular matrix or, conversely, causes fibrosis to set in. Prolonged exposure to ultraviolet radiation, particularly radiation of A and B type, has the effect of stimulating the expression of collagenases, particularly of MMP1. This is one of the components of photo-induced ageing of the skin. Hypertrophy of the adipose tissue is accompanied, at the dermal level, by the fibre network being placed under tension, leading to a functional deterioration of the resident cells. Indeed, this hypertension impedes cellular exchanges and venous and lymphatic circulation by compression of capillaries, so that the phenomenon is self-maintaining. In the end, the fibres degenerate and the skin loses its fundamental structures.

From the biological point of view, when the fibroblasts are subjected to a normal tissue tension, they actively synthesize collagen, elastin and glycosaminoglycans, which are essential molecules that contribute to reinforcing the supporting tissues of the skin. Similarly, adipocytes overloaded with lipids also exert a tension on the dermis, leading to overproduction of collagen until fibrosis occurs. This is reflected, in clinical terms, by skin which is more consistent and taut.

On the other hand, during weight loss, and in particular during slimming diets, the rapid destorage of the adipocytes leads to a considerable decrease in the tension exerted by the hypodermis on the supporting tissues. Consequently, since the dermis is no longer under tension, the connective tissue gradually loses its cohesion: loss of attachment of the fibroblasts to the collagen, decrease in the amount of neocollagen, distension of elastin fibres, depolymerization of proteoglycans.

Consequently, the fibroblasts, which have less interaction with the fibres of the extracellular matrix, no longer receive from their environment the activity and repair signals which control the synthesis of the essential macro molecules of the dermis. In addition, the fibroblasts which are no longer receiving signals from their fibrillar environment secrete matrix metalloproteases (MMPs), enzymes that result in degradation of the fibrous structures. This marked slowing of the fibroblast metabolism and also the degradation of the fibres by the MMPs is consequently reflected by a deterioration of the viscoelastic or biomechanical properties of the skin (loss of firmness, of tonicity, of elasticity, etc).

On reading the above, it is possible to understand the importance of collagen and glycosaminoglycans in the structure of tissues, in particular of the skin and/or the mucous membranes, and the importance of combating degradation thereof in order to thus combat ageing, whether it is chronological or photo-induced ageing, and the consequences thereof, in particular on thinning of the dermis and/or degradation of collagen fibres, the latter consequence leading in particular to the appearance of flaccid skin, the object of the present invention being precisely to combat this.

In overweight individuals, and more generally during weight gain, the adipocytes have a tendency to rapidly increase in volume (storage of increasing amounts of lipids). The fat lobules then distend little by little so as to result in the formation of connective trabeculae, parallel to one another and perpendicular to the skin surface. The strong pressure exerted by the adipocytes on the dermis rapidly causes a deformation of the surface of the skin.

In cutaneous terms, this "cellulite" phenomenon is reflected by a padded appearance giving, in places, signs of "orange peel".

Finally, from the clinical point of view, cellulite is reflected by a modification of the texture of the subcutaneous and superficial tissues, characterized in particular by:

- skin which, overall, is thicker,

- skin which is more consistent,

- skin which is more sensitive, and which can even, depending on the stage of progression of the cellulite, be painful on palpation, and/or - cutaneous tissues which are less mobile due to the loss of adhesion and of cohesion of the deep layers of skin.

Thus, this phenomenon is more visible in women since they have finer skin with connective trabeculae exhibiting a vertical structure, which, conversely, in men have an oblique and criss-cross structure.

Cellulite, which is often worsened by excess weight and obesity, is especially located around the hips and the lower limbs ("jodhpur thigh" or "zouave pants" cellulite). These modifications can also result in definitive scar formations, in particular in areas most subject to variations in adipose tissue mass, such as the buttocks, the hips, the stomach or the top of the legs.

Hypertrophy of the adipose tissue, associated in particular with weight gain, is accompanied, at the dermal level, by the fibre network being placed under tension, leading to a functional deterioration of the resident cells. Indeed, this hypertension impedes cellular exchanges and venous and lymphatic circulation by compression of capillaries, so that the phenomenon is self-maintaining. In the end, the fibres degenerate and the skin loses its fundamental structures. The occurrence of an uneven ("orange peel") skin, of more or less flaccid or gelatinous consistency, can also gradually give the figure an unsightly general appearance. Furthermore, the development of the adipose mass can evolve between simple local excess weight (lipodysmorphia) and the formation of cellulite, passing through a certain level of stoutness and ending at actual obesity. Obesity is, on the other hand, a real disabling pathological condition when it results in particular in the development of a metabolic syndrome that the combination which is the subject of the invention does not, however, intend to treat since it addresses only aesthetic disorders of the figure which are not associated with a pathological condition.

Likewise, consequences are also visible at the surface of the skin during weight loss which is sometimes too fast and in particular during slimming diets. Indeed, the rapid destorage of the adipocytes leads to a considerable decrease in the tension exerted by the hypodermis on the supporting tissues. When these weight gain and weight loss variations follow on from one another, the term "yo-yo" effect is used. The appearance of cicatricial marks, also called stretch marks, which are the sign that the dermal tissue has been affected and has not been able to adapt to these overly large and overly rapid changes in adipose mass in the underlying hypodermis, may sometimes follow.

In biological terms, an inflammatory state of the adipose tissue may be observed during adipose tissue hypertrophy. Inflammation of the adipose tissue, in particular of the subcutaneous white adipose tissue (ScWAT) has been particularly well described in the case of obesity. Indeed, when the energy balance of the body is unbalanced, either through a lack of physical exercise or through excessive consumption of food (or both), the subcutaneous adipose tissue expands and accumulates under the skin. When this significant development of the adipose mass is maintained, a more general metabolic imbalance may follow. The adipose tissue is in fact considered, as a whole, to be an important endocrine organ, the physiology of which may be impaired by adipose cell hypertrophy and the accumulation of peri-adipocyte immune cells, including in particular macrophages. It has thus been described that the pre-adipocytes of non-obese women respond to the factors produced by these macrophages and produce molecules and chemokines such as IL-8 and MCP1 which further amplify and maintain the adipose tissue inflammation by recruiting further inflammatory cells into the adipose tissue (D. Lacasa et al. Endocrinology 148(2):868-87 (2007); M. Keophiphat et al. Molecular endocrinology 23: 11-24 (2009).

As an expected and ubiquitous physiological consequence of such a chronic inflammatory state associated in particular with an overly large development or else with an overly fast variation in size of the adipose tissue (both upwards and downwards), a "pro-fibrotic" phenotype may then develop in the inflammatory adipose tissue. When this pro-fibrotic phenotype develops more particularly in the subcutaneous white adipose tissue (scWAT), it contributes to the setting in of the observable sign of deterioration at the actual skin surface, which is in particular cellulite.

Indeed, among many identified aetiological factors, cellulite appears to be due to structural, morphological, inflammatory and biochemical deteriorations of the subcutaneous adipose tissue (Khan et al. Treatment of cellulite; part II advances and controversies J Am Acad Dermatol 373-384 (2010)). Macroscopically, cellulite is characterized by a moderate increase in the thickness of the dermis (+18%), but especially of the hypodermal adipose tissue (x 3.2), and by strong indentations of the adipose tissue as far down as the dermis (B.Querleux; Cellulite; pathophysiology and treatment; Taylor and Francis group London Chapter 6 pp 105-113 (2006). As an expected consequence of the inflammatory deteriorations of the subcutaneous adipose tissue, fibrotic shapes which are the result of a deep rearrangement of the peri-adipocyte tissue are observed: women who have cellulite thus show a greater number of fibrous septae perpendicular to the surface of the skin in comparison with the subcutaneous adipose tissue of women without cellulite (p<0.001; B. Querleux et al. Skin research and Technology; 8: 118-124 (2002)).

As illustrated in the examples of the present application, the inventors have noted that petroselinic acid or a combination of active agents in accordance with the invention proves to be capable of synergistically increasing the amount of lipoxin A4. Lipoxin A4 belongs to the resolvin family. This family of compounds naturally produced by the body acts in a manner complimentary to the conventional anti-infiammatories by raising the threshold triggering a "dermato logically conventional" inflammatory response, and more particularly so as to raise the threshold of appearance of the signals of this conventional inflammation, namely redness, pain and heat. Consequently, lipoxin A4 appears to be a potential target for acting on these skin parameters.

Consequently, the present invention is more particularly focused on identifying active agents or combinations of active agents which exert a significant action on lipoxin A4 .

The use of petroselinic acid for preparing a composition intended for activating the peroxisomal β-oxidation of fatty acids in the superficial tissues of a mammal, so as to be able to treat or prevent inflammations and/or modulate lipid metabolism in these superficial tissues, is known from document EP 888 773. The skin conditions more particularly targeted in said document are inflammations associated with psoriasis, erythema (sunburn), eczema, seborrhoeic dermatitis, alopecia areata, mycosis, acne or other forms of dermatosis.

Thus, none of the documents suggests that petroselinic acid exerts an activity on lipoxin A4.

The first subject of the invention is thus the use, topically or by injection, of petroselinic acid or of a combination of active agents, comprising at least petroselinic acid, in accordance with the invention, for combating effects, in particular non-pathological effects, on the adipose tissue, and in particular for combating aesthetic disorders of the figure associated with adipose tissue modifications.

A subject of the invention is also the use of petroselinic acid or of a combination of active agents, comprising at least petroselinic acid, in accordance with the invention, topically or by injection, for reducing the weight of body fat of an individual.

The expression "reducing the weight of body fat of an individual" is intended to mean a reduction of body fat of at least 1% in an individual after 6 weeks of use, preferably at least 2%, preferably at least 3%, preferably at least 4%, preferably at least 5%, preferably at least 10%.

The body fat of an individual can be measured by any means known to those skilled in the art, in particular by impedance analysis. According to the present invention, the term "body fat" is intended to denote the mass of adipose tissue, or fat, in an individual, as opposed to the muscle mass.

A subject of the invention is also the use of petroselinic acid or of a combination of active agents, comprising at least petroselinic acid, in accordance with the invention, topically or by injection, for reducing the total weight of an individual.

The expression "reducing the total weight of an individual" is intended to mean a reduction of the total weight of at least 1% in an individual after 6 weeks of use, preferably at least 2%, preferably at least 3%, preferably at least 4%, preferably at least 5%, preferably at least 10%.

A subject of the invention is also the use of petroselinic acid or of a combination of active agents, comprising at least petroselinic acid, in accordance with the invention, with a view to limiting the expansion of or reducing the adipose tissue, in particular subcutaneous adipose tissue.

The expression "reducing the adipose tissue of an individual" is intended to mean a reduction of the adipose tissue of at least 1% in an individual after 6 weeks of use, preferably at least 2%, preferably at least 3%, preferably at least 4%, preferably at least 5%, preferably at least 10%. A subject of the invention is also the use, topically or by injection, of petroselinic acid or of a combination of active agents, comprising at least petroselinic acid, in accordance with the invention, for improving the figure by limiting or reducing, in particular, the unsightly accumulations of subcutaneous adipose tissue at the level of the waist, the hips, the thighs, the stomach, the arms and the face.

The expression "reducing the unsightly accumulations of subcutaneous adipose tissue of an individual" is intended to mean a reduction of the subcutaneous adipose tissue of at least 1% in an individual after 6 weeks of use, preferably at least 2%, preferably at least 3%), preferably at least 4%, preferably at least 5%, preferably at least 10%>. The measurement of the reduction in subcutaneous adipose tissue can be carried out by measuring the loss of centimetres at the level of the waist, the hips, the thighs, the stomach or the arms, or else by any method known to those skilled in the art. A subject of the invention is also the cosmetic use, topically or by injection, of petroselinic acid or of a combination of active agents, comprising at least petroselinic acid, in accordance with the invention, for combating cellulite. In particular, a subject of the invention is the use, topically or by injection, of petroselinic acid or of a combination of active agents, comprising at least petroselinic acid, in accordance with the invention, for preventing and/or treating the visual manifestations of cellulite and/or the orange peel appearance and/or else for treating stretch marks or preventing the occurrence thereof.

A subject of the invention is also the use, topically or by injection, of petroselinic acid or of a combination of active agents, comprising at least petroselinic acid, in accordance with the invention, for the purposes of combating the signs of deterioration of the skin surface during a variation in weight, both upwards and downwards, in particular during weight loss especially observed in the course of a slimming diet or during weight loss observed prior to, simultaneously with and/or subsequent to a plastic surgery procedure.

The invention also targets the use, topically or by injection, of petroselinic acid or of a combination of active agents, comprising at least petroselinic acid, in accordance with the invention, with a view to maintaining and/or restoring the biomechanical properties of the skin, in particular chosen from the extensibility, tonicity, firmness, suppleness, density and/or elasticity properties of the skin.

In particular, the invention relates to the use, topically, of petroselinic acid or of a combination of active agents, comprising at least petroselinic acid, in accordance with the invention, with a view to maintaining and/or restoring the extensibility, tonicity, firmness, suppleness, density and/or elasticity properties of the skin.

The invention also targets the use, topically or by injection, of petroselinic acid or of a combination of active agents, comprising at least petroselinic acid, in accordance with the invention, with a view to preventing and/or combating skin disorders induced by weight loss, in particular observed during a slimming diet.

The invention also targets the use, topically or by injection, of petroselinic acid or of a combination of active agents, comprising at least petroselinic acid, in accordance with the invention, as an agent for firming the skin of a subject having undergone a weight modification or prior to, simultaneously with and/or subsequent to a plastic surgery procedure.

The invention also targets the use, topically or by injection, of petroselinic acid or of a combination of active agents, comprising at least petroselinic acid, in accordance with the invention, with a view to preventing and/or combating skin disorders in particular observed during excessive weight gain.

The invention also targets the use, topically or by injection, of petroselinic acid or of a combination of active agents, comprising at least petroselinic acid, with a view to preventing and/or combating adipose tissue expansion and weight gain resulting in an unsightly modification of the figure.

When the active agent is suitable for the topical route, it may in particular be used in a cosmetic composition.

When the active agent is suitable for injection, it may in particular be used in a pharmacological composition.

The invention also relates to a method for preventing and/or combating effects on the adipose tissue, comprising the oral administration, to an individual, of petroselinic acid or of a combination of active agents, comprising at least petroselinic acid, in accordance with the invention.

The invention also targets a method for combating cellulite, comprising the oral administration, to an individual, of petroselinic acid or of a combination of active agents, comprising at least petroselinic acid, in accordance with the invention.

The invention also relates to a method for combating the signs of deterioration of the skin surface during a variation in weight, both upwards and downwards, comprising at least the administration, topically or by injection, to an individual, of petroselinic acid or of a combination of active agents, comprising at least petroselinic acid, in accordance with the invention.

The methods according to the invention have the characteristics of cosmetic methods insofar as they make it possible to improve the attractiveness of the figure, in particular by combating cellulite and the unsightly accumulations of subcutaneous adipose tissue. In particular, the methods according to the invention comprising topical administration are clearly in the cosmetics field and therefore outside the therapeutic field.

In addition, a cosmetic composition according to the invention may be used daily for several months, without medical prescription. The present invention therefore clearly lies outside the therapeutic field.

In the context of the present invention, the "cellulite" is the result of fat storage in the adipocytes and/or water retention in the dermis and the hypodermis. There is often additionally an inflammation of the subcutaneous connective tissues. In the context of the present invention, the expression "viscoelastic or biomechanical properties of the skin" is intended to mean the extensibility, tonicity, firmness, suppleness and/or elasticity properties of the skin.

The expression "aesthetic disorders of the figure" is intended to mean a skin disorder induced by weight-loss and/or slimming diets and a skin disorder induced by cellulite.

The expression "skin disorder induced by weight-loss and/or slimming diets" is intended to mean all the modifications of the external appearance of the skin, for instance the flaccid skin appearance that can be more or less marked following weight loss.

The expression "skin disorder induced by cellulite" is intended to mean all the modifications of the external appearance of the skin, for instance the nodes of fat or "orange peel" which can be more or less localized in the areas of excess weight, such as the thighs, the arms or the abdomen.

The term "preventing" is intended to mean "reducing the risk of developing". The term "treating", unless otherwise indicated, is intended to mean any action that aims to improve the comfort or the well-being of an individual; this term therefore covers both attenuating or relieving and curing.

The weight modification, and in particular weight loss, may be due to a slimming diet or to pregnancy.

The plastic surgery procedure may be chosen from lifting, liposuction and the injection of filling products. Petroselinic acid

According to a first embodiment variant, the petroselinic acid, (CI 8: 1 n-12 or cis delta 6) monounsaturated fatty acid or CI 8 delta-6-cis-octadecenoic acid, may be used in an isolated form.

According to another variant of the invention, the petroselinic acid is used in the form of a plant extract containing same, such as an oil. This form is particularly suitable for the topical mode of administration or the mode of administration by injection.

The petroselinic acid-rich oils are more particularly chosen from umbellifer oils.

The expression "petroselinic acid-rich oil" is intended to mean an oil comprising at least 40% of petroselinic acid.

The umbelliferae are plants of which the flowers are parasol-shaped; the species which are particularly petroselinic acid-rich are Umbellifarea-Apiacea and Araliaceae. Plants of the Thapsia genus are also sources of petroselinic acid (Avato et al, Lipids, 2001, 36, 845).

The species preferably used in the invention are coriander, chervil, carrot, celery, cumin, caraway, parsley and dill, or mixtures thereof. The petroselinic acid-source umbellifer oil which is quite particularly suitable for the invention may be extracted from the seed of these umbellifers, for example by milling or pressing, and then refining

The umbellifer oil has a petroselinic acid content which varies according to the umbellifer seed from which it is extracted. For the same umbellifer, the petroselinic acid content also varies according to the country of origin of the umbellifer and according to the extraction which may be more or less complete.

Petroselinic acid is also an abundant compound (approximately 40%) of the

Geranium sanguineum seed oil.

In particular, the petroselinic acid may be used in the form of umbellifer oil or

Geranium sanguineum oil.

Thus, according to one embodiment, the umbellifer oil more particularly considered in the invention may be chosen from dill, parsley, caraway, cumin, celery, carrot, chervil and coriander seed oils, and mixtures thereof.

Preferably, the petroselinic acid is used in the form of a coriander seed oil.

According to the present invention, the coriander seed oils are covered by the expressionn

"coriander oil". The contents are variable depending on whether the combination of active agents in accordance with the invention is used in a cosmetic composition intended for topical administration or administration by injection.

The petroselinic acid content, in a cosmetic composition intended for topical administration or administration by injection, in accordance with the invention, may be between 0.01% and 70%> by weight, in particular between 0.1 % and 70%> by weight, and particularly between 1% and 70% by weight, relative to the total weight of the composition or of the food supplement.

The petroselinic acid content in a cosmetic composition intended for topical administration or administration by injection, in accordance with the invention, may be such that the daily dose of said petroselinic acid is between 0.5 and 2000 mg/d, particularly between 1 and 1000 mg/d, and in particular between 5 and 700 mg/d.

The active agent or the combination of active agents, comprising at least petroselinic acid, in accordance with the present invention, may also be used with additional active agents suitable for the mode of administration considered, as is described hereinafter.

The active agent or the combination of active agents, comprising at least petroselinic acid, in accordance with the invention, may be used with additional active agents, in any one of the routes of administration, chosen from (i) lipolysis modulators, for instance methylxanthines (caffeine, theophylline, aminophylline) or phosphatidylcholine and also hormones and extracts of plants such as guarana or konjac, or (ii) inflammation modulators, for instance Omega 3 and Omega 6 polyunsaturated fatty acids, gamma- lino leic acid and oils comprising same, such as echium oil, vitamins B3 niacin/niacinamide and B8, anti- inflammatory peptides, for instance KPV(Lysine Proline Valine); vitamin D3.

ADMINISTRATION BY INJECTION

A composition intended for administration by injection has a duty to be administered in a form free of viable or revivable, potentially infectious, microbial germs known to those skilled in the art. In order to meet this requirement, a composition in accordance with the invention may be subjected, in a combined or separate manner, to a sterilization process according to one of the conventional methods well known to those skilled in the art, for instance heating in an autoclave, or ionizing irradiation, such as electron beams and gamma rays.

An injection is an instrumental method used for parenterally introducing into the organism a liquid substance for therapeutic purposes, by means of a hollow needle which goes through the upper layer of the skin.

The composition intended for administration by injection may be injected by mesotherapy or intra-hypodermally.

Mesotherapy is a technique of treatment via intraepidermal and/or intradermal and/or subcutaneous injection of active product(s).

The composition comprising the combination of active agents, comprising at least petroselinic acid, in accordance with the invention, is administered according to this technique by injection in the form of multiple small droplets into the epidermis, the dermal-epidermal junction and/or the dermis in order in particular to perform subcutaneous layering. The mesotherapy technique is in particular described in the book "Traite de mesotherapie" ["Treatise on mesotherapy"] by Jacques LE COZ, published by Masson, 2004.

Mesotherapy carried out on the face is also known as a mesolift or also as mesoglow.

There are several injection techniques. For example, in the case of an injection by mesotherapy, micropuncture (needle pricks close together) or multipoint (needle pricks at several points further apart) may be used.

The repeated injections may also be carried out point by point manually. The needle prick points may be separated, for example, by a distance ranging from 5 mm to 1 cm.

According to one embodiment, the administration can be carried out in several sessions at intervals of a few days, for example 1, 2, 3, 4, 5 or 6 days, to a few weeks, for example 1, 2, 3 or 4 weeks.

According to one embodiment, the administration-by- injection step(s) may be advantageously carried out by means of an injection gun, in particular a high injection frequency, hydropneumatic-compression injection gun. TOPICAL ADMINISTRATION

The expression "composition administered or applied topically" is intended to mean dermocosmetic compositions comprising a combination of active agents in accordance with the invention which may be in the form of a salve, creams, milks, ointments, powders, impregnated pads, solutions, gels, sprays, lotions or suspensions. They may also be in the form of lipid or polymeric microspheres, nanospheres or vesicles or polymer patches and hydrogels allowing a controlled release, but also patches or masks for local use. These topically administered compositions may be either in anhydrous form or in aqueous form.

As regards the products intended to be applied in particular to the skin, they may be aqueous, aqueous-alcoholic or oily solutions, dispersions of the solution type or dispersions of the lotion or serum type, emulsions of liquid or semi-liquid consistency of the milk type, suspensions or emulsions of the cream type, aqueous or anhydrous gels, microemulsions, microcapsules, microparticles, or vesicular dispersions of ionic and/or non- ionic type.

The cosmetic compositions, more particularly relating to topical application, may in particular be in the form of aqueous, aqueous-alcoholic or oily solutions, dispersions of the solution type or dispersions of the lotion or serum type, emulsions of liquid or semi-liquid consistency of the milk type, obtained by dispersing a fatty phase in an aqueous phase (O/W), or vice versa (W/O), or suspensions or emulsions of soft, semisolid or solid consistency of the cream type, aqueous or anhydrous gels, or alternatively microemulsions, microcapsules, microparticles, or vesicular dispersions of ionic and/or non-ionic type. These compositions are prepared according to the usual methods.

These compositions may in particular constitute cleansing, protective, treating or care creams for the face, the hands, the feet, the major anatomical folds or the body (for example day creams, night creams, makeup-removing creams, foundation creams or antisun creams), makeup products such as fluid foundations, makeup-removing milks, protective or care body milks, after-sun milks, skincare lotions, gels or mousses, for instance cleansing or disinfectant lotions, antisun lotions or artificial tanning lotions, bath compositions, deodorant compositions containing a bactericidal agent, aftershave gels or lotions, hair-removing creams, or compositions for combating insect stings. The compositions in which the combination of active agents, comprising at least petroselinic acid, in accordance with the invention, can be used may also consist of solid preparations constituting soaps or cleansing bars.

When the composition is an emulsion, the proportion of the fatty phase may range from 5% to 80% by weight and preferably from 5% to 50% by weight relative to the total weight of the composition. The oils, emulsifiers and coemulsifiers used in the composition in emulsion form are chosen from those conventionally used in the cosmetics field. The emulsifier and the coemulsifier may be present in the composition in a proportion ranging from 0.3% to 30% by weight and preferably from 0.5% to 20% by weight relative to the total weight of the composition.

When the composition is an oily solution or gel, the fatty phase may represent more than 90% of the total weight of the composition.

In a known manner, the cosmetic composition may also contain adjuvants that are common in the cosmetics field, such as hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic active agents, preserving agents, antioxidants, solvents, fragrances, fillers, screening agents, bactericides, odour absorbers and colorants. The amounts of these various adjuvants are those conventionally used in the field under consideration, and are for example from 0.01% to 20% of the total weight of the composition. Depending on their nature, these adjuvants may be introduced into the fatty phase and/or into the aqueous phase.

As fatty substances that may be used in the invention, mention may be made of mineral oils, for instance hydrogenated polyisobutene and liquid petroleum jelly, plant oils, for instance a liquid fraction of shea butter, sunflower oil and apricot kernel oil, animal oils, for instance perhydrosqualene, synthetic oils, in particular purcellin oil, isopropyl myristate and ethylhexyl palmitate, and fluoro oils, for instance perfluoropolyethers. It is also possible to use fatty alcohols, fatty acids, for instance stearic acid, and for instance waxes, in particular paraffin wax, carnauba wax and beeswax. It is also possible to use silicone compounds, for instance silicone oils and for example cyclomethicone and dimethicone, and silicone waxes, resins and gums. These compounds may or may not be functionalized.

As emulsifiers that may be used in the invention, mention may be made, for example, of glyceryl stearate, polysorbate 60, the mixture of cetylstearyl alcohol/cetylstearyl alcohol oxyethylenated with 33 mol of ethylene oxide sold under the name Sinnowax AO® by the company Henkel, the mixture of PEG-6/PEG-32/glycol stearate sold under the name Tefose® 63 by the company Gattefosse, PPG-3 myristyl ether, silicone emulsifiers such as cetyl dimethicone copolyol, and sorbitan monostearate or tristearate, PEG-40 stearate and oxyethylenated (20 EO) sorbitan monostearate.

As solvents that may be used in the invention, mention may be made of lower alcohols, in particular ethanol, isopropanol, and propylene glycol.

Hydrophilic gelling agents that may be mentioned include carboxylic polymers such as carbomer, acrylic copolymers such as acrylate/alkyl acrylate copolymers, polyacrylamides and in particular the mixture of polyacrylamide, C13-14 isoparaffin and laureth-7 sold under the name Sepigel 305® by the company SEPPIC, polysaccharides, for instance cellulose derivatives such as hydroxyalkyl celluloses and in particular hydroxypropyl cellulose and hydroxyethyl cellulose, natural gums such as guar gum, locust bean gum and xanthan gum, and clays.

Lipophilic gelling agents that may be mentioned include modified clays, for instance bentones, metal salts of fatty acids, for instance aluminium stearates and hydrophobic silica, or else ethyl cellulose and polyethylene.

According to one variant of the invention, the combination of active agents, comprising at least petroselinic acid, in accordance with the present invention, may be used in a topical composition also comprising at least one agent for stimulating the dermal macro molecules and/or for preventing degradation thereof.

As active agent for stimulating the dermal macromolecules or for preventing degradation thereof, mention may be made of those which act:

- either on collagen synthesis, for instance synthetic peptides, such as iamin, biopeptide CL or palmitoyloligopeptide sold by the company Sederma; peptides extracted from plants, such as the soya hydro lysate sold by the company Coletica under the trade name Phytokine^®; and plant hormones, such as auxins and lignans;

- or on elastin synthesis, such as the Saccharomyces cerevisiae extract sold by the company LSN under the trade name Cytovitin^®; and the extract of the alga Macrocystis pyrifera sold by the company Secma under the trade name Kelpadelie^®; - or on glycosaminoglycan synthesis, such as the product of fermentation of milk by Lactobacillus vulgaris, sold by the company Brooks under the trade name Biomin yogourth®; the extract of the brown alga Padina pavonica sold by the company Alban Miiller under the trade name HSP3®; and the Saccharomyces cerevisiae extract available in particular from the company Silab under the trade name Firmalift® or from the company LSN under the trade name Cytovitin®;

- or on fibronectin synthesis, such as the extract of the zooplankton Salina sold by the company Seporga under the trade name GP4G®; the yeast extract available in particular from the company Alban Miiller under the trade name Drieline®; and the palmitoyl pentapeptide sold by the company Sederma under the trade name Matrixil®;

- or on the inhibition of serine proteases, such as leukocyte elastase or cathepsin G. Mention may be made of: the peptide extract of legume (Pisum sativum) seeds, sold by the company LSN under the trade name Parelastyl^®; heparinoids; and pseudodipeptides, such as {2-[acetyl-(3-trifluoromethylphenyl)amino]-3- methylbutyrylamino } acetic acid.

Moreover, the administration of the combination of active agents, comprising at least petroselinic acid, in accordance with the present invention, may advantageously be combined with radio frequency procedures, draining procedures, the application of ultrasound, laser treatments and/or physical methods of massage such as endermology or liposuction according to techniques known to those skilled in the art.

The compositions according to the invention may also comprise at least one carotenoid other than lycopene, in particular a carotenoid chosen from β-carotene, astaxanthin, zeaxanthin and lutein, flavonoids such as catechins, hesperidin, proanthocyanidins, in particular in the form of blackcurrant seed oil, anthocyanins, ubiquinones, coffee extracts containing polyphenols and/or diterpenes, chicory extracts, ginkgo biloba extracts, proanthocyanidin-rich grape extracts, pimento extracts, soya bean extracts, other sources of flavonoids with antioxidant properties, fatty acids, prebiotics, probiotics, resveratrol, selenium amino acids and glutathione precursors.

In other words, one to three compositions may be administered per day. A composition for topical administration or injection may advantageously contain, as cosmetic active agent, an additional active agent chosen from vitamin C, glucosamine, collagen and hyaluronic acid, and mixtures thereof.

Still as cosmetic active agent other than the combination of active agents, comprising at least petroselinic acid, in accordance with the invention, a cosmetic composition for administration topically or topically may advantageously also contain at least one inhibitor of matrix degradation, for instance extracts of rosemary, rosmarinic acid; carnosic acid; curcumin; pine bark extract; pycnogenol; berberine; Boswellia extracts; emodin; sesamol; sulforaphane and broccoli extracts; resveratrol and grape extracts; 6-shogaol; blackcurrant extracts; aubergine extracts; enterolactone; Loquat extracts; olive extracts, for instance oleuropein; pachymic acid, pterostilbene, hydroxytyrosol, and mixtures thereof.

Needless to say, those skilled in the art will take care to select the optional compound(s) to be added to the compositions in accordance with the invention and also the concentration thereof, such that the advantageous properties intrinsically associated with the compositions in accordance with the invention are not, or are not substantially, adversely affected by the envisaged addition.

Moreover, the administration of the active agent, in addition to the petroselinic acid, in accordance with the present invention, may advantageously be combined with radio frequency procedures, draining procedures, the application of ultrasound, laser treatments and/or physical methods of massage such as endermology or liposuction according to techniques known to those skilled in the art.

Other characteristics and advantages of the invention will emerge more clearly from the examples that follow, which are given as non-limiting illustrations.

Example 1

Demonstration of the inhibitory effect of the petroselinic acid according to the invention on the basal synthesis/release of lipoxin A4 by keratinocytes compared with a control without coriander oil (0%) Level of

Compounds tested lipoxin A4

production

Coriander oil

(including between

60% and 75% of +19%

petroselinic acid)

0.25 mg/ml

Example 2:

Such a composition in accordance with invention may in particular have the following contents:

% by weight relative to the total weight

Constituents

of the composition

Petroselinic acid 54.9 (provided by the coriander seed oil)

Zinc gluconate 6.3 (including 13.6% of active material)

18.7 (including 98.5 % of active

Taurine

material)

Vitamin E 1.0 (including 67 % of active material)

Vitamin D3 0.03 (including 2.5 % of active material)

Claims

1. Cosmetic use, topically, of petroselinic acid for combating aesthetic disorders of the figure associated with adipose tissue modifications.

2. Cosmetic use, topically, of petroselinic acid for limiting the expansion of and/or reducing the adipose tissue, in particular subcutaneous adipose tissue.

3. Use according to either of the preceding claims, for reducing the weight of body fat of an individual.

4. Use according to one of the preceding claims, for reducing the total weight of an individual.

5. Use according to one of the preceding claims, for improving the figure by limiting or reducing, in particular, the unsightly accumulations of subcutaneous adipose tissue at the level of the waist, the hips, the thighs, the stomach, the arms and the face.

6. Use according to one of the preceding claims, for combating cellulite.

7. Use according to one of the preceding claims, for preventing and/or treating the visible manifestations of cellulite and/or the orange peel appearance and/or else for treating stretch marks or preventing the occurrence thereof.

8. Cosmetic use according to one of the preceding claims, for combating the signs of deterioration of the skin surface during a variation in weight, both upwards and downwards, in particular during weight loss especially observed in the course of a slimming diet or during weight loss observed prior to, simultaneously with and/or subsequent to a plastic surgery procedure.

9. Use according to one of the preceding claims, for maintaining and/or restoring the biomechanical properties of the skin, in particular chosen from the extensibility, tonicity, firmness, suppleness, density and/or elasticity properties of the skin.

10. Use according to any one of the preceding claims, in which said petroselinic acid is used in an isolated form or in the form of a plant extract containing same, in particular in the form of an oil.

11. Use according to any one of the preceding claims, in which said petroselinic acid is used in the form of umbellifer oil or Geranium sanguineum oil.

12. Use according to the preceding claim, in which said umbellifer oil is chosen from dill, parsley, caraway, cumin, celery, carrot, chervil and coriander seed oils, and mixtures thereof, preferably in the form of a coriander seed oil.

13. Cosmetic use according to any one of the preceding claims, in which the combination of active agents is used in a composition.

14. Cosmetic use according to any one of the preceding claims, in which the composition is a cosmetic composition.

15. Cosmetic method for combating aesthetic disorders of the figure associated with adipose tissue modifications, comprising the administration, topically, of petroselinic acid to an individual.