JP2009516670A - Cosmetic use of tension agents to improve skin thickness and / or complexion brightness - Google Patents

Abstract

  Cosmetic use of a composition comprising at least one mosaic effect tensioning agent to increase skin thickness in a physiologically acceptable medium.

Description

  The present invention relates to the field of skin care and in particular to the improvement of skin appearance and / or complexion.

  The present invention particularly addresses the beauty of a composition comprising an effective amount of at least one mosaic effect tensioning agent in a physiologically acceptable medium to improve skin thickness and / or enhance facial brightness. Related to general use.

  The present invention further provides an effective amount of at least one mosaic effect tension agent as an agent intended to improve skin firmness and / or elasticity and / or tension in a composition comprising a physiologically acceptable medium. Concerning cosmetic use.

  The invention is similarly dull and / or well defined, including topical application of a composition comprising at least one mosaic effect tension agent to a person with a dull and / or poorly defined complexion. The present invention relates to a cosmetic processing method for no complexion.

  This type of mosaic effect is particularly selected from (i) mineral tensioning agents and (ii) tensioning polymers.

  The present invention is particularly directed to facial and / or neck skin treatments. However, the compositions of the present invention can also be applied to areas of the body that exhibit a loss of elasticity and / or stiffness, such as the abdomen and thigh.

  The skin constitutes a physical barrier between the body and its surrounding environment. The skin is composed of two tissues: the epidermis and the dermis.

  The epidermis is a keratinized multilayered epithelium that is constantly metabolized. Keratinocytes constitute the primary epidermal cell population and are responsible for maintaining the epithelial structure and its barrier function. The epidermis is supported by a cell-free basement membrane called the dermal epidermal junction that ensures adhesion with the dermis.

  The epidermis is composed of several cell layers, the deepest part of which is the basal layer composed of undifferentiated cells. Over time, these cells differentiate and move toward the surface of the epidermis, thereby forming various epidermal layers, and finally dead cells that are removed by desquamation on the surface of the epidermis. Will form keratinocytes. This surface loss is compensated by the movement of cells from the basal layer to the epidermis surface. This process is one of the continuous metabolisms of the skin.

  The dermis is an elastic and compressible connective support tissue derived from the mesoderm, an extracellular matrix composed mainly of fibroblasts and fibrous proteins (collagen and elastin) and non-fibrotic proteins (proteoglycans and glycoproteins) Consists of. The dermis is the supporting tissue of the epidermis, but also plays an important role in the development and growth of the epidermis and its differentiation. Fibroblasts and extracellular matrix also affect the mechanical properties of the skin, in particular its elasticity, tension and firmness. Fibroblasts and extracellular matrix also affect skin density.

  Homeostasis of the skin, especially the epidermis, arises from a finely regulated balance between the process of skin cell proliferation and differentiation. These growth and differentiation processes are fully regulated: these processes are involved in skin metabolism and / or regeneration and lead to the maintenance of a constant skin thickness, especially a constant epidermal thickness. This skin homeostasis is also involved in maintaining the mechanical properties of the skin.

  However, this skin homeostasis can be affected by certain physiological factors (age, menopause, hormones, etc.) or environmental factors (UV stress, pollution, oxidative stress, irritant stress, etc.). The possibility of epidermal regeneration is lessened: cell differentiation in the basal layer is reduced, which leads in particular to slowing and / or reducing epidermal metabolism. Consequently, cell metabolism no longer compensates for the loss of cells removed at the surface, with epidermal atrophy and / or skin thickness reduction and / or elasticity and / or tension and / or stiffness. Cause loss.

  These clinical signs are visible in the skin of the face and / or neck, but also in areas of the body that exhibit a loss of stiffness and / or elasticity, such as the body, especially the abdomen and / or thigh. It is also visible on the skin.

  Changes in epidermal homeostasis also appear as a non-bright and / or unclear outline appearance on the skin complexion.

This phenomenon can become more pronounced with menopause: women complain that their skin has hardened and dried, or even develops xeroderma. Hormone deficiency associated with menopause is particularly accompanied by a decrease in metabolic activity, which can cause decreased keratinocyte proliferation and increased epidermal differentiation.
International Patent Application No. 98/29091 French patent application No. 2823113 French patent application 2843024 French patent application No. 2655551 U.S. Patent No. 3819825 U.S. Pat. No. 4,777041 French Patent Application No. 2816315 International Patent Application No. 03/008438 International Patent Application No. 03/007905 International Patent Application No. 03/077936 French Patent Application No. 2829025 French patent application No. 2828810 U.S. Pat. No. 6,703,027 U.S. Pat.No. 5,175,279 U.S. Patent No. 6,139,322 U.S. Patent No. 6465001 U.S. Pat. International Patent Application No. 98/29092 International Patent Application No. 2005067884 European Patent Application No. 1038519 European Patent Application No. 0582152A International Patent Application No. 93/23009 International Patent Application No. 95/03776 EP1043345 French patent application No. 2819429 JP-A-2-295912 US 5977215 U.S. Pat.No. 5,521,246 Pommerenke et al., Eur J Cell Biol, June 1996, 70 (2): 157-64. Fujiwara et al., Cell struct funct February 2001, 26 (1): 11-17 Li et al., Cell Signal July 2000; 12 (7): 435-45 Perrin et al. (Int J Tissue React, 2004; 26 (3-4): 97-104. Smith-Waterman local homology algorithm (1981, Ad.App. Math., 2: 482) Neddleman-Wunsch local homology algorithm (1970, J. Mol. Biol., 48: 443) Pearson-Lipman similarity search method (1988, Proc. Natl. Acad. Sci. USA, 85: 2444) Tenaud et al., British Journal of Dermatology, 1999: 140; pp. 26-34 Edited by Peter HARRIS, Elsevier, 1989 book "Food Gels" Chapters 3, 1 and 6 Haake et al., Exp Cell Res., February 25, 1997; 231 (1) 83-95. Mazzalupo et al., February 2003; 226 (2): 356-65 Asselineau et al. (1987 Models in dermato., Vol.III, Ed. Lowe & Maibach, 1-7)

  Therefore, what is needed is to maintain and / or increase the thickness of the skin, particularly the face and / or neck skin, and to maintain and / or improve the mechanical properties of the skin, particularly the face and / or neck skin, It is understood to have an agent capable of improving skin homeostasis in order to improve complexion.

  The prior art discloses the use of soluble cosmetic agents to improve cellular metabolism. These drugs include, for example, retinoic acid derivatives, in particular retinol, also known as vitamin A, and esterified derivatives of retinol, which have the effect of promoting the growth of keratinocytes and inhibiting their differentiation. Thereby facilitating epidermal metabolism, increasing the thickness of the epidermis and / or improving the radiance of the complexion.

  Soluble cosmetic agents act classically through binding to receptors that elicit intracellular responses, resulting in regulation of the expression of proteins involved in epidermal proliferation and / or differentiation processes. This is referred to as a direct “biological” effect.

  Applicants have now surprisingly and unexpectedly improved skin homeostasis and / or complexion with a biomechanical effect provided by topical application of effective amounts of cosmetic agents, particularly tension agents. It may be obtained through

  Applicants have shown in practice that topical application of an effective amount of a tensioning agent, such as an acrylic copolymer, to a reconstructed skin model has the effect of modulating the expression of proteins involved in skin homeostasis.

  According to the present invention, a “biomechanical effect” is a cosmetic that induces a biological response in epidermal and / or dermal cells via a mechanical effect that is effective at the surface of the skin (stratum corneum). It means the ability of drugs, especially tension agents.

  “Mechanical effects that are effective at the surface of the skin” are biologically effective mechanical stretches, ie, mechanical stretches that are capable of transmitting mechanical perturbations from cell to cell or through the extracellular matrix. It means the ability of a cosmetic agent to induce mechanical elongation including the activation of mechano-receptors present in the cell membrane. These cells are referred to as “biologically sensitive to mechanical stretch” and are of particular interest to epidermal and dermal cells, especially keratinocytes and fibroblasts.

  These mechanical stretches are between the extracellular matrix and the cell via membrane receptors or “mechano-receptors”, in contrast to conventional triggering effects by the types of soluble molecules used so far. Or has the effect of regulating the equilibrium established between two adjacent cells.

  Mechanical stretch is transmitted into cells in the form of biochemical signals via membrane receptors or mechano receptors.

  These mechanoreceptors are membrane receptors that are sensitive to mechanical stretch, in other words membrane receptors that can induce intracellular biological responses in response to mechanical perturbations. The mechanoceptors include integrins (Pommerenke et al., Eur J Cell Biol, June 1996, 70 (2): 157-64), PECAM1 receptors (Fujiwara et al., Cell struct funct February 2001, 26 (1): 11-17) or PDGF growth factor receptor (Li et al., Cell Signal July 2000; 12 (7): 435-45).

  Stretch triggers activation of multiple second messengers in the first step by inducing mechanical perturbations of these receptors. Elongation activates, among other things, protein tyrosine kinase (PTK), protein kinase C (PKC), G proteins rac and cdc42, or induces release of calcium flux. These various signaling pathways result in the activation of protein kinases from a single family, MAP kinases, Erk1, Erk2 and p38. Once activated, MAPK induces the activation of specific transcription factors that regulate the expression of numerous genes involved in keratinocyte homeostasis. These activation mechanisms are also well regulated: in the process of elongation, in particular Erk induces the expression of MAPK phosphatase known to suppress Erk. This process allows cells to control the signal induced by elongation and prevent pathological overgrowth of keratinocytes.

  To the best of Applicants' knowledge, epidermal homeostasis, especially skin thickness and / or complexion, is improved by topically applying to the skin an effective amount of a cosmetic agent with biomechanical effects, particularly a tensioning agent. There is no statement or suggestion to date.

  The prior art discloses the use of tensioning agents to obtain a superficial and immediate visual effect that relieves microrelief of the skin, in particular wrinkles and fine lines. These agents are described as being able to form films that cause contraction of the stratum corneum, the stratum corneum on the surface of the epidermis. The use of such polymer-based cosmetic or dermatological agents to reduce skin microrelief changes with age is described in International Patent Application No. 98/29091. Other tensioning agents may be inorganic, as described, for example, in French Patent Application No. 2823113, French Patent Application No. 2843024 and French Patent Application No. 2655951 or U.S. Pat. No. 3819825 and U.S. Pat. It consists of a dispersion of colloidal particles, especially silica. Another tensioning agent is a mixed silicate such as that described in French patent application 2816315.

  However, to the best of Applicants' knowledge, the ability to modulate the biological effects of tensioning agents, particularly the ability to regulate the expression of proteins involved in skin homeostasis, or skin homeostasis, especially to improve skin thickness And / or to improve the complexion of the complexion and / or to improve the mechanical properties of the skin, not only at the face and / or neck level, but also in certain areas of the body (e.g. abdomen, thighs) No description of their use at the level of part) exists to date.

  The present invention therefore particularly provides the cosmetic use of a composition comprising at least one mosaic effect tensioning agent for increasing skin thickness in a physiologically acceptable medium.

  The present invention also provides the cosmetic use of a composition comprising at least one mosaic effect tensioning agent to increase the thickness of the epidermis in a physiologically acceptable medium.

  The present invention further provides the cosmetic use of a composition comprising in a physiologically acceptable medium at least one mosaic effect tensioning agent for improving facial color brightness.

  The present invention further provides the cosmetic use of a composition comprising in a physiologically acceptable medium at least one mosaic effect tensioning agent for promoting the regeneration and / or reconstitution of the nipple dermis.

  The invention also provides the cosmetic use of an effective amount of at least one mosaic effect tensioning agent as an agent intended to improve skin homeostasis in a composition comprising a physiologically acceptable medium.

  In particular, an effective amount of at least one mosaic effect tensioning agent is intended to improve epidermal homeostasis.

  The term “effective amount of tensioning agent” that can be used according to the present invention obtains an effect on the modulation of the expression of genes involved in the homeostatics of the skin, particularly the biological effects required of tensioning agents, especially in the context of the present invention Means a sufficient amount.

This effective amount or effective dose can be assessed by DNA array methods, for example as described in the illustrative examples below, the general principle of which is as follows:
-Applying different doses of tensioning agent to cells or epidermis model and / or reconstructed skin in culture;
-Extracting mRNA from said treated or untreated (control) cells and performing "reverse" transcription using, for example, oligo dT and P33-labeled deoxynucleotide triphosphate to label the target cDNA sequence;
-Hybridize these target cDNA sequences to a dedicated minichip containing DNA specific for markers involved in skin cell physiology, particularly skin homeostasis (called `` cDNA probes '');
-After washing, the amount of labeled target sequence is measured and compared to the control to assess the difference in expression of the target gene induced by local application of the tensioning agent to the control;
-Subsequently, there are differences in the expression of genes involved in proliferation (increase) and / or differentiation (decrease) in skin cells compared to the (untreated) control. Selection of the amount and associated effective dose is made. Advantageously, compared to controls, genes involved in keratinocyte differentiation (e.g. corneodesmosine, loricrin, suprabasin) expression and / or genes involved in skin regeneration (e.g. cytokeratin) The relevant effective dose is selected that results in an increase in), preferably a difference in expression of more than 2 times compared to the control.

  The tensioning agent is included in the composition of the present invention in an amount ranging from 0.01% to 30% by weight as the active ingredient, preferably from 1% to 30% by weight as the active ingredient, based on the total weight of the composition. It's okay. 2% to 30% by weight, in particular 3% to 20% by weight, preferably 4% to 20% by weight as active ingredient relative to the total weight of the composition, for example as active ingredient relative to the total weight of the composition It would be particularly possible to use an effective amount of tensioning agent in the range of 6% to 10% by weight. According to one particular embodiment, the effective amount of tensioning agent is 3% to 20% by weight as active ingredient relative to the total weight of the composition, preferably 3% as active ingredient relative to the total weight of the composition. % To 7% by weight.

  The intent by the “active ingredient” is to exclude media in which the tensioning agent is optionally solubilized or in its commercial form as in the case of dispersions of colloidal particles.

  The present invention also provides an effective amount of at least as an agent intended to increase skin thickness, particularly epidermal thickness, in a composition for topical application to the skin comprising a physiologically acceptable medium. Provide cosmetic use of one mosaic effect tension agent.

  The present invention also provides an effective amount as an agent intended to enhance facial brightness and / or improve light intensity in a composition for topical application to the skin comprising a physiologically acceptable medium. Provide cosmetic use of at least one mosaic effect tension agent.

  The present invention also improves and / or improves the mechanical properties of the skin in a composition for topical application to the skin comprising a physiologically acceptable medium, in particular the firmness and / or elasticity of the skin and A cosmetic use of an effective amount of at least one mosaic effect tensioning agent as an agent intended to improve the improvement of tension is provided.

  The present invention also relates to an effective amount of at least one mosaic effect tension agent as an agent intended to improve skin density in a composition for topical application to the skin comprising a physiologically acceptable medium. Provide cosmetic use.

  The present invention also relates to an effective amount of at least one of the agents intended to promote the regeneration and / or reconstitution of the nipple dermis in a composition for topical application to the skin comprising a physiologically acceptable medium. Provides cosmetic use of two mosaic effect tension agents.

  The present invention also provides an effective amount of at least as an agent intended to promote extracellular matrix regeneration and / or reconstitution in a composition for topical application to the skin comprising a physiologically acceptable medium. Provide cosmetic use of one mosaic effect tension agent.

  The present invention also contemplates delaying the process of epidermal differentiation and / or promoting skin regeneration and / or neogenesis in a composition for topical application to the skin comprising a physiologically acceptable medium. The cosmetic use of an effective amount of at least one mosaic effect tensioning agent is provided.

  Mosaic effect tensioning agents may be contemplated by the present invention for one or more conditions selected from those described above.

  An effective amount of at least one mosaic effect tensioning agent present in the composition is intended to delay the process of epidermal differentiation and / or promote skin regeneration and / or neoplasia.

The biological effect of tension agents shown by the applicant is a continuous biological effect, as opposed to the rapid visual effects known to date as tension agents.
The continued biological effect is particularly explained by the fact that the mechanical stress induced by the tension agent in the stratum corneum affects the entire skin tissue: within the epidermis, keratinocytes become increasingly dynamic to neighboring cells In the dermis, mechanical stress is transmitted to cells, especially fibroblasts, through the extracellular matrix. Thus, mechanical stress converts this mechanical signal into a biochemical signal and then propagates into the cell via mechanoreceptors involved in the regulation of gene expression involved in the overall homeostasis of the tissue.

The continuous or long-term effect obtained on skin homeostasis, in particular skin thickness, may be optimized by application twice a week, preferably daily, of the composition according to the invention.
This continuous or long-term effect through the repeated application of the mosaic effect tension agent may be described as follows: Physiological regulation of tissue by tension agents, on the other hand, at the molecular level, keratinocytes and fibroblasts Is the result of regulation in the synthesis and synthesis of proteins involved in the differentiation and proliferation of the matrix, on the other hand in the organization of the matrix. In order for molecular regulation to have macroscopic results, they need to be accumulated. As a result, as with all biological stimuli, it is necessary to repeat the stimulation of the tensioning agent in order for the tensioning agent to lead to reconstitution of the skin tissue.

  An effective amount of at least one mosaic effect tensioning agent applied to the surface layer of the skin regulates the expression of genes involved in skin homeostasis, especially via radio waves of mechanical tension involved in activation of mechanoreceptors Contemplate.

  A “mosaic effect tensioning agent” that can be used according to the present invention means a compound that has a tension effect, in other words that can stretch the skin and is reliable to have a mosaic effect as described below.

  Generally, the tensioning agent is soluble in water according to the present invention at a temperature in the range of 25 ° C. to 50 ° C. at a concentration of 7% by weight in water, or at a maximum concentration that forms a medium of uniform appearance Refers to any compound that is or disperses and produces a shrinkage of greater than 15% in water at this 7% concentration or at this maximum concentration in the tests described below.

  The maximum concentration that forms a medium with a uniform appearance is determined to be ± 10%, preferably ± 5%.

  A “medium having a uniform appearance” means a medium that does not exhibit an aggregate that can be identified with the naked eye.

  To determine the maximum concentration, the tensioning agent is gradually added to the water while stirring using a deflocculator device at a temperature in the range of 25 ° C. to 50 ° C., and then the mixture is kept stirring for 1 hour. A test is then carried out after 24 hours in order to determine whether the mixture thus prepared has a uniform appearance (no aggregates visible with the naked eye).

  The tension effect may be characterized by an in vitro contraction test.

  A uniform mixture of tensioning agents is prepared beforehand as described above at a concentration of 7% by weight in water or at the maximum concentration defined above.

30 μl of the homogeneous mixture is placed on an elastomeric rectangular specimen (10 × 40 mm, thus having an initial width W _{0 of} 10 mm) having a modulus of elasticity of 20 MPa and a thickness of 100 μm.

After drying for 3 hours at 22 ± 3 ° C., relative humidity (RH), 40 ± 10%, the elastomer specimen shows a shrinkage of the width recorded as W _3h due to the extension exerted by the applied tension agent .

  The tension effect (TE) of the drug is then quantified as follows:

  Furthermore, the tensioning agent according to the invention must be a mosaic effect tensioning agent.

  The mosaic effect tensioning agent, according to the present invention, when applied to a glass plate, dries to form a mosaic deposit, and the size and shape of the tessera that composes it may depend on its position relative to the edge of the deposit. There is.

  “Mosaic attachment” more precisely means a discontinuous attachment composed of a very large number of small individual domains or microdomains.

Tessera or microdomains are generally small in size. This size may range from 0.1 mm ² to several mm ² .

  In particular, this type of mosaic-like attachment is in contrast to continuous or semi-continuous attachment that adheres to the substrate and can be separated or detached as a single piece or into two or more relatively large sized pieces, There is no possibility of peeling or separation from the substrate.

  Furthermore, this type of mosaic deposit is generally less resistant to water, in other words, the deposit collapses when in contact with water.

  This type of mosaic deposit according to the present invention is shown in FIG.

  The tessellar or mosaic appearance of adhesion is particularly attributed to the fact that the stress generated during the drying process by these tensioning agents is greater than the cohesive force (rigidity) of adhesion.

  From a mechanical point of view, this type of adhesion formed by these mosaic effect tensioning agents may be characterized by their rupture properties under stress, which is evaluated, for example, in the mechanical strength test described below.

In particular, the mosaic effect tensioning agent of the invention advantageously has a breaking energy between 0 and 20 J / m ² (preferably equal to 0) and between 0 and 0.2 mm in the mechanical strength test described below. It forms an adhesion characterized by destructive deformation.

  The mechanical strength test consists essentially of applying a compressive stress, for example, to the point of failure of the tension agent on the surface of the flexible deformable foam.

  The tensioning agent is added to the water at a concentration of 7% by weight in water or at a maximum weight concentration that forms a medium having a uniform appearance in water at a temperature in the range of 25 ° C to 50 ° C.

  The use of this foam substrate makes it possible to apply considerable deformations to the tensioning agent attached to the surface and thus to quantify its breaking strength. The mechanical compressive stress is given by a cylindrical punch having a diameter of 1 mm, and the displacement rate of the punch is 0.1 mm / second.

The test is performed using a TA-XT2i texture analyzer sold by Stable Micro System. In this way, a curve of the force F (unit N) is obtained as a function of the displacement d (unit mm), and from this, as shown in Fig. 2, the breakdown point of substance (tension agent) or J / m ² It is possible to determine the fracture energy W _break expressed.

The fracture energy W _break represented by J / m ² corresponds to the area under the curve F = f (d) obtained at the deformation value at which the stop F _break (N) is observed.

  The mosaic effect tensioning agent used according to the invention is able to distribute the stretch it exerts more fully over the entire surface area of the skin compared to continuous or semi-continuous deposition. Compared to other tensioning agents that adhere to a flexible substrate such as the skin to form a continuous or semi-continuous adhesion. This is because in the case of continuous or semi-continuous adhesion sticking to a flexible substrate, stretching occurs only on the substrate in the vicinity of the solid adhesion.

  In contrast, in the case of the mosaic attachment of the present invention, with the same surface area as the above attachment, stretching occurs around each independent tessera of the attachment, thereby significantly increasing the surface area subject to stretching.

  This stretch, which distributes more effectively across the entire surface area of the skin where adhesions are formed, has allowed applicants to show that biological effects can be obtained even more quickly: the mosaic effect tensioning agent Starting from the first few hours after application to the skin, especially 48 hours later.

  This type of mosaic effect tensioning agent according to the present invention may be selected from (i) mineral tensioning agents, and (ii) tensioning polymers, and mixtures thereof.

The mineral tensioning agent may be selected from:
a) mixed silicates;
b) inorganic filler colloidal particles;
And mixtures thereof.

  The mosaic effect tensioning polymer may be selected from synthetic polymers and mixtures thereof.

  Those skilled in the art will know how to select from the above chemical categories substances that meet the tension test described above.

  These various categories of tensioning agents will be described herein.

(i) Mineral tension agent
-Mixed silicates This expression is of natural or synthetic origin comprising at least two different cations selected from alkali metals (e.g. Na, Li, K) or alkaline earth metals (e.g. Be, Mg, Ca) and transition metals Means all silicates.

It is preferable to use a phyllosilicate, that is, a silicate having a structure in which a SiO ₄ tetrahedron is formed in a sheet shape and a metal cation is included between the sheets.

  A particularly preferred silicate class as a tensioning agent is laponite. Laponite is a magnesium lithium sodium silicate having a layer structure similar to montmorillonite. Laponite is a synthetic form of a natural mineral known as hectorite. Laponite sold under the name Laponite XLS or Laponite XLG by Rockwood can be used, for example.

-Colloidal particles of inorganic fillers "Colloid particles" are numbers between 0.1 and 100 nm, preferably between 3 and 30 nm, in aqueous, water-alcohol or alcoholic media, preferably in dispersions in aqueous media. It means particles having an average diameter.

The colloidal particles of the present invention have no thickening properties in water, alcohol, oil and all other solvents. The viscosity of the solution thus obtained at a concentration of 15% by weight or more in water is less than 0.05 Pa · s at a shear rate of 10 s ⁻¹ . The measurement is performed at 25 ° C. using a cone / plate-shaped Haake RheoStress RS150 rheometer, and the measurement values of the measurement cone are as follows: diameter 60 mm, angle 2 °.

  These particles are generally different from fumed silica particles, which are generally prepared by a sol-gel process and are therefore agglomerated in water to form larger aggregates.

  Inorganic filler colloidal particles that can be used in accordance with the present invention are generally silica, cerium oxide, zirconium oxide, alumina, calcium carbonate, barium sulfate, calcium sulfate, zinc oxide and titanium dioxide colloidal particles, platinum colloidal particles , Mixed colloidal particles, eg, selected from titanium dioxide such as silica-coated titanium dioxide and one or more coatings. It is preferred to use colloidal silica or colloidal silica-alumina composite particles in the composition of the present invention.

Colloidal particles of silica In the present patent application, colloidal silica means colloidal particles of silica in a dispersion in an aqueous, water-alcohol or alcoholic medium. The silica colloidal particles have a diameter in the range of 0.1 to 100 nm, preferably 3 to 30 nm. These particles exist in the form of an aqueous dispersion and do not have any thickening properties in water, alcohols, oils and all other solvents. The viscosity of the solution thus obtained at a concentration of 15% by weight or more in water is less than 0.05 Pa · s at a shear rate of 10 s ⁻¹ . The measurement is performed at 25 ° C. using a cone / plate-shaped Haake RheoStress RS150 rheometer, and the measurement values of the measurement cone are as follows: diameter 60 mm, angle 2 °.

  Colloidal silicas that can be used in the compositions of the present invention include, for example, those sold by Catalysts & Chemicals under the names Cosmo S-40 and Cosmo S-50.

Colloidal Silica-Alumina Composite Particles The colloidal particles of inorganic filler that can be used in accordance with the present invention may also be selected from colloidal silica-alumina composite particles. Silica-alumina composite refers to silica particles in which aluminum atoms are partially arranged in place of silica atoms. Colloidal particles in this patent application mean colloidal particles in dispersion in an aqueous, water-alcohol or alcoholic medium. The colloidal silica-alumina composite particles have a diameter in the range of 0.1 to 100 nm, preferably 3 to 30 nm. These particles exist in the form of an aqueous dispersion and do not have any thickening properties in water, alcohols, oils and all other solvents. The viscosity of the solution thus obtained at a concentration of 15% by weight or more in water is less than 0.05 Pa · s at a shear rate of 10 s ⁻¹ . The measurement is performed at 25 ° C. using a cone / plate-shaped Haake RheoStress RS150 rheometer, and the measurement values of the measurement cone are as follows: diameter 60 mm, angle 2 °.

  At pH 7, the colloidal silica-alumina composite particles of the present invention have a zeta potential of less than -20 mV, preferably less than -25 mV. The measurement is performed at 25 ° C. using a Coulter Scientific Instrument DELSA 440SX instrument.

  Colloidal silica-alumina composite particles that can be used in the compositions of the present invention include, for example, those sold by Grace under the names Ludox AM, Ludox AM-X 6021, Ludox HSA, and Ludox TMA.

  The preferred mineral tensioning agent according to the invention is colloidal particles of silica. And colloidal particles selected from colloidal silica-alumina composite particles. In particular, those marketed under the names of Cosmo S-40 and Cosmo S-50 and those marketed under the names of Ludox AM, Ludox HAS, and Ludox TMA can be mentioned.

  Preferred colloidal particles of inorganic filler are selected from colloidal particles of silica.

(ii) Tension polymer The tension polymer used according to the present invention is generally a synthetic polymer.

  Those skilled in the art will know from the chemical categories of polymers described below how to select polymers that produce the mosaic effect described above and meet the mechanical strength test described above.

In particular, the polymers of the present invention form an adhesion characterized by a fracture energy between 0 and 20 J / m ² and a fracture deformation between 0 and 0.2 mm in the mechanical strength test described above.

  The synthetic polymers used in accordance with the present invention are in the form of solutions or suspensions in polar or nonpolar (latex) liquids, preferably aqueous or aqueous dispersions, or dry forms redispersible in cosmetic solvents. It's okay.

  Synthetic polymers that can be used as tensioning agents may be selected from acrylic polymers. The synthetic polymer according to the invention may in particular be selected from an interpenetrating polymer network (IPN).

  These polymers may take the form of random linear copolymers, interpenetrating polymer networks (IPNs), and block polymers, among others. Regardless of its type, the synthetic polymeric tensioning agent may have a weight average molecular weight Mw in the range of 3,000 to 1,000,000 Da.

Random linear copolymers Random linear copolymers that are tension agents in the sense of the present invention have a linear ethylene backbone with a molecular weight of less than 600,000 Da (g / mol), preferably between 15,000 and 600,000 g / mol. A monomer selected from random copolymers and having a glass transition temperature Tg above 40 ° C. (preferably> 60 ° C.), the corresponding homopolymer being at least 70% and at least one monomer insoluble in water at 25 ° C. Contains ionic hydrophilic monomers. The copolymer may also contain a minor proportion of monomers having a Tg of less than 40 ° C.

  These copolymers generally exhibit an overall glass transition temperature of 45 ° C. or higher.

All copolymers composed of:
70% to 90% by weight of at least one aryl or alkyl acrylate and / or at least one aryl or alkyl methacrylate and / or styrene listed below 10% to 30% (meth) acrylic acid.

  List of preferred alkyl (meth) acrylates; benzyl acrylate, cyclohexyl acrylate, tert-butyl acrylate, isobornyl acrylate and norbornyl acrylate, methyl, ethyl, isobutyl, cyclohexyl, benzyl, tert-butyl, isobornyl and norbornyl methacrylate Preferably methyl methacrylate and cyclohexyl methacrylate.

Particularly preferred among the above polymers:
A copolymer of methyl methacrylate / methacrylic acid; a copolymer of methyl methacrylate / acrylic acid, said copolymer comprising between 70% and 90% by weight of methyl methacrylate;
-An ethyl methacrylate / methacrylic acid copolymer; an ethyl methacrylate / acrylic acid copolymer, said copolymer comprising between 70% and 90% by weight of ethyl methacrylate;
An isobutyl methacrylate / methacrylic acid copolymer; an isobutyl methacrylate / acrylic acid copolymer, said copolymer comprising between 70% and 90% by weight of isobutyl methacrylate;
A copolymer of benzyl methacrylate / methacrylic acid; a copolymer of benzyl methacrylate / acrylic acid, said copolymer comprising between 70% and 90% by weight of benzyl methacrylate;
A copolymer of benzyl acrylate / methacrylic acid; a copolymer of benzyl acrylate / acrylic acid, said copolymer comprising between 70% and 90% by weight of benzyl acrylate;
A copolymer of cyclohexyl methacrylate / methacrylic acid; a copolymer of cyclohexyl methacrylate / acrylic acid, said copolymer comprising between 70% and 90% by weight of cyclohexyl methacrylate;
A copolymer of cyclohexyl acrylate / methacrylic acid; a copolymer of cyclohexyl acrylate / acrylic acid, said copolymer comprising between 70% and 90% by weight of cyclohexyl acrylate;
a copolymer of tert-butyl methacrylate / methacrylic acid; a copolymer of tert-butyl methacrylate / acrylic acid, said copolymer comprising between 70% and 90% by weight of tert-butyl methacrylate;
a copolymer of tert-butyl acrylate / methacrylic acid; a copolymer of tert-butyl acrylate / acrylic acid, said copolymer comprising between 70% and 90% by weight of tert-butyl acrylate;
An isobornyl methacrylate / methacrylic acid copolymer; an isobornyl methacrylate / acrylic acid copolymer, said copolymer comprising between 70% and 90% by weight of isobornyl methacrylate;
An isobornyl acrylate / methacrylic acid copolymer; an isobornyl acrylate / acrylic acid copolymer, said copolymer comprising between 70% and 90% by weight of isobornyl acrylate;
A copolymer of norbornyl methacrylate / methacrylic acid; a copolymer of norbornyl methacrylate / acrylic acid, the copolymer comprising between 70% and 90% by weight of norbornyl methacrylate;
A copolymer of norbornyl acrylate / methacrylic acid; a copolymer of norbornyl acrylate / acrylic acid, the copolymer comprising between 70% and 90% by weight of norbornyl acrylate;
-A copolymer of styrene / methacrylic acid; a copolymer of styrene / acrylic acid, said copolymer comprising between 70% and 90% by weight of styrene,
It is.

  The copolymer according to the invention is in the form of a dispersion in a polar liquid. These copolymers are dispersed in water after neutralization with a base.

  Preferred copolymers according to the invention are selected from methyl methacrylate / methacrylic acid copolymers, said copolymer comprising between 70% and 90% by weight of methyl methacrylate.

Interpenetrating polymer or IPN
In the present invention, an “interpenetrating polymer network” is a mixture of two comb polymers obtained by simultaneous polymerization and / or cross-linking of two types of monomers, and the resulting mixture has a single glass transition temperature. It means a mixture having. Examples of IPNs suitable for use in the present invention and processes for preparing them are described, for example, in US Pat. No. 6,139,322 and US Pat. No. 6,465,001. Preferably, the IPN according to the present invention comprises at least one acrylic polymer, and more preferably further comprises at least one polyurethane or copolymer of vinylidene fluoride and hexafluoropropylene. According to a preferred embodiment, the IPN according to the invention comprises a polyurethane and an acrylic polymer. This type of IPN is in particular the Hybridur series IPN marketed by Air Products. A particularly preferred IPN is in the form of an aqueous dispersion of particles having a weight average size between 90 and 110 nm and a number average size of about 80 nm. The IPN preferably has a glass transition temperature Tg in the range of about -60 ° C to + 100 ° C. This type of IPN is sold under the trade name Hybridur 875, in particular by Air Products. Reference is made to Hybridur X01602 and Hybridur 580 as other IPNs suitable for use in the present invention.

  Other IPNs suitable for use in the present invention include IPNs composed of a mixture of polyurethane and a copolymer of vinylidene fluoride and hexafluoropropylene. These IPNs can be prepared especially as described in US Pat. No. 5,534,003. As a variant, IPN is a KYNAR RC-10, 147 and KYNAR RC by ATOFINA in the form of a colloidal dispersion in water with a fluorocopolymer ratio between 70:30 and 75:25 to acrylic polymer. -10, 151 marketed under the trade name.

Block Polymer As a variant, the synthetic polymer tensioning agent that can be used in the composition of the invention may be a block polystyrene (PS) -polyethyl acrylate (PEA) polymer.

  Very generally, block copolymers are polymers composed of at least two separate homopolymers, each composed only of monomers A and B. Accordingly, the blocks of the present invention are polystyrene (PS) and polyethyl acrylate (PEA) blocks, respectively.

  In the context of this variant, the polymer is a PS-PEA-PS type triblock polymer, or type PS- [PEA-PS] n, or PEA-, where n is a positive integer, preferably 1. It may be a multiblock polymer of [PS-PEA] n. Advantageously, these block polymers are linear copolymers. The molecular weight of the polymer is preferably greater than 10,000 daltons, more preferably greater than 50,000 daltons. The weight ratio of PS and PEA monomers may be defined such that PS / PEA is greater than 1, preferably PS / PEA is greater than 5.

Mention may be made of the triblock polymers PS (30,000) -PEA (10,000) -PS (30,000) which are most particularly suitable for the practice of the present invention. This particularly advantageous block copolymer is a triblock copolymer comprising:
-A first block comprising units derived from styrene and having a number average molecular weight of 30,000 g / mol;
-A second block composed of units derived from ethyl acrylate and having a number average molecular weight of 10,000 g / mol;
A third block comprising units derived from styrene and having a number average molecular weight of 30,000 g / mol.

  Copolymers meeting the above definition are those in which the first block and / or the third block, preferably the first block and the third block, are derived from methacrylic acid in addition to units derived from styrene. It may be a copolymer comprising units, for example in a 98/2 (styrene / methacrylic acid) weight ratio.

  The synthetic copolymer used according to the invention may alternatively be composed of random polystyrene polyethyl acrylate copolymer. The weight ratio of PS and PEA monomers is defined to be PS / PEA> 1, preferably PS / PEA> 5.

  The synthetic polymer used according to the present invention comprises (a) 70% to 90% by weight of at least one alkyl acrylate and / or at least one alkyl methacrylate and / or styrene, and (b) 10% to 30% by weight. Are preferably selected from acrylic copolymers comprising at least one copolymer of at least one ionic hydrophilic monomer.

  In particular, the synthetic polymer is an ethylenic copolymer.

  Another preferred synthetic polymer is an interpenetrating polymer network type polymer, particularly an interpenetrating polymer network comprising a polyurethane polymer and an acrylic polymer.

  More preferably, the use of an interpenetrating polymer containing polyurethane and an acrylic polymer is mentioned.

  The present invention also provides a cosmetic composition comprising at least one interpenetrating polymer network for enhancing and / or improving skin firmness and / or elasticity and / or tension in a physiologically acceptable medium. Regarding use.

  The invention also relates to the cosmetic use of a composition comprising at least one interpenetrating polymer network to promote extracellular matrix regeneration and / or reconstitution in a physiologically acceptable medium.

  The present invention also relates to the cosmetic use of a composition comprising at least one interpenetrating polymer network in a physiologically acceptable medium to promote skin regeneration and / or neogenesis.

  In particular, the interpenetrating polymer network includes polyurethane and acrylic polymer.

  The mosaic effect tensioning agent will be present in the composition in an amount effective to obtain the biological effect required by the present invention.

  By way of example, the mosaic effect tensioning agent is in the composition according to the invention in the range from 0.01% to 30% by weight, preferably from 1% to 30% by weight as the active ingredient, relative to the total weight of the composition. May be included in any amount.

  2% to 30% by weight, in particular 3% to 20% by weight, preferably 4% to 20% by weight as active ingredient relative to the total weight of the composition, in particular as active ingredient relative to the total weight of the composition It may be particularly possible to use an effective amount of tensioning agent in the range of 3% to 7% by weight, for example in the range 6% to 10% by weight as active ingredient relative to the total weight of the composition.

  According to one particular embodiment, an effective amount of tensioning agent will be used at 3% to 20% by weight as the active ingredient relative to the total weight of the composition.

  The intent by the “active ingredient” is to exclude media in which the tensioning agent is optionally solubilized or in its commercial form as in the case of dispersions of colloidal particles.

  The composition of the invention comprises a physiologically acceptable medium, in other words a medium that is compatible with the face and / or body skin. It is preferably a cosmetically acceptable medium, in other words it has a pleasant color, odor and feel and any unacceptable discomfort (stinging) that may cause the user to give up using this composition. It is a medium that does not produce a feeling of tension or redness.

  The composition of the present invention may be a body care or facial care composition or a makeup composition.

  The composition of the present invention may be any of the formulation forms conventionally used for topical application, especially in the form of an aqueous gel or lotion type dispersion, dispersing the fatty phase in the aqueous phase (O / W) or vice versa. (W / O) emulsions with milk-type liquid or semi-liquid consistency, or suspensions or emulsions with soft, semi-solid or solid consistency, cream or gel type, or serum or stick Or a multi-phase emulsion (W / O / W or O / W / O), a microemulsion, an ionic and / or non-ionic vesicle dispersion, or a wax / water phase dispersion. . These compositions are prepared according to the usual methods.

Oils that can be used in the compositions of the present invention include:
-Animal-derived hydrocarbon oils such as perhydrosqualene;
-Plant-derived hydrocarbon oils, such as liquid triglycerides of fatty acids containing 4 to 10 carbon atoms, or vegetable oils such as, for example, apricot kernel oil and shea butter oil;
-Synthetic esters and ethers, in particular branched or unbranched hydrocarbon chains in which R ¹ represents a fatty acid residue containing 8 to 29 carbon atoms and R ² contains 3 to 30 carbon atoms Representing fatty acids such as oils of formula R ¹ COOR ² and R ¹ OR ² ;
-Mineral or synthetic derived linear or branched hydrocarbons such as volatile or non-volatile liquid paraffin and their derivatives, isohexadecane, isododecane, petrolatum, polydecene, Parleam® (Pearl Ream) oil, etc. Hydrogenated polyisobutene;
-Natural or synthetic essential oils;
-Branched fatty alcohols containing 8 to 26 carbon atoms, such as octyldodecanol;
-Partially hydrocarbon-modified and / or silicone-modified fluorine oils such as those described in document JP-A-2-295912;
-Silicone oils, e.g. volatile or non-volatile polydimethylsiloxanes (PDMS) with linear or cyclic silicone chains that are liquid or pasty at ambient temperature, in particular cyclopolydimethylsiloxanes (cyclomethicone), e.g. cyclohexa Siloxanes and cyclopentasiloxanes; polydimethylsiloxanes containing alkyl, alkoxy or phenyl groups as pendant or at the end of the silicone chain, where these groups contain 2 to 24 carbon atoms, such as phenyl trimethicone, phenyl dimethicone Phenyltrimethylsiloxydiphenylsiloxane, diphenyldimethicone, diphenylmethyldiphenyltrisiloxane, 2-phenylethyltrimethylsiloxysilicate and polymethylphenylsiloxane; and
-A mixture of these.

  Other fatty substances that may be present in the oil phase are, for example, fatty acids containing 8 to 30 carbon atoms such as stearic acid, lauric acid, palmitic acid and oleic acid; linear chains such as cetyl alcohol and / or stearyl alcohol A fatty fatty alcohol; a pasty fatty substance such as lanolin; a wax; a gum such as silicone gum (dimethiconol).

  These fatty substances may be variously selected by skilled workers in order to prepare compositions having the desired properties, such as consistency or feel.

  The composition comprises various adjuvants commonly used in the cosmetics field, such as esters of fatty acids and polyethylene glycol, optionally polyoxyethylenated fatty acids and sorbitan, polyoxyethylene fatty alcohols and fatty acids and sucrose. Or emulsifiers such as esters or ethers of sugars such as glucose; fillers; preservatives; sequestering agents; fragrances; and thickeners and / or gelling agents such as homopolymers and copolymers of acrylic acid, homopolymers of acrylamide and Copolymers and / or 2-acrylamido-2-methylpropane sulfonic acid (AMPS), modified AMPS (Aristoflex LNC and SNC) products, and xanthan gum may further be included.

  Fillers include, for example, polyamide (Nylon) particles in the form of spheres or microfibers; polymethyl methacrylate microspheres; ethylene-acrylate copolymer powders; foamed powders such as hollow microspheres, especially vinylidene chloride, acrylonitrile and methacrylate terpolymers Microspheres formed and sold under the name Expancel; powders of natural organic substances, such as starch powders, in particular cross-linked or non-cross-linked corn, wheat or rice starch powders, such as starch powder cross-linked with octenyl succinic anhydride Silicone resin microbeads such as those sold under the name Tospearl by Toshiba Silicone; Silica; Metal oxides such as titanium dioxide or zinc oxide; Mica; By Takemoto Oil and Fat Hollow hemispherical particles silicones such NLK506 sold; and mixtures thereof.

  Of course, those skilled in the art will recognize these optional options so that the advantageous properties of the compositions of the present invention are not adversely affected by any or all of the intended additions. Will carefully select the compound to be added and / or its amount.

  The composition according to the invention is applied to the skin to be cared for, for example by cream, gel, serum or lotion, in particular the skin of the body, face and / or neck, according to typical techniques.

  The invention also features applying a composition comprising an effective amount of at least one mosaic effect tensioning agent in a physiologically acceptable medium to a person with a dull and / or less defined complexion. A cosmetic treatment method for dull and / or less well defined complexion is provided.

  Similarly, part of the context of the present invention is to apply a composition comprising an effective amount of at least one mosaic effect tension agent in a physiologically acceptable medium to a person with soft and / or sagging skin, or A method of cosmetic treatment of soft and / or sagging skin, characterized in that it is applied to areas of the body that have lost elasticity and / or stiffness.

  In particular, it would be possible to apply the composition to the face and / or neck, abdomen and thighs.

  Advantageously, it is possible to apply the composition according to the invention twice a week, more preferably daily, in the morning and / or evening, in order to obtain a continuous effect of tension agents on skin homeostasis Will.

  The present invention also provides a method for cosmetic treatment of skin comprising the application of a composition comprising at least 3% by weight of at least one mosaic effect tensioning agent, at a frequency of at least twice a week, relative to the total weight of the composition. provide.

  In particular, the composition comprises 3 to 30%, preferably 3 to 7% by weight of at least one mosaic effect tensioning agent, based on the total weight of the composition.

  More preferably, the composition is applied to the skin at a frequency of at least once a week.

  The effects on skin mechanical properties, particularly skin firmness, elasticity, and extensibility, by repeated application of the tensioning agent of the present invention to the skin were also confirmed in vivo by an instrumental device as described below. And / or could be evaluated.

Torque meter:
This device is intended to measure skin extensibility, firmness / elasticity and tension variation. The device applies a twisting force to the skin plane for a certain time; then stretches the skin, which corresponds to the extensibility (Ue) of the skin; Therefore, the tension (Ur) is evaluated. The firmness / elasticity of the skin corresponds to the ratio Ur / Ue (tension / extension).

Cute meter:
A cute meter is a suction device composed of a cylinder with a diameter of 1 to 3 mm applied to the skin. By pulling up the skin by means of a pump connected to the cylinder, a vertical displacement of the skin is brought about, thereby allowing an evaluation of the mechanical properties of the skin.

Densiscore:
Density score is a device that allows the measurement of skin density. A fold is generated by applying mechanical stress locally to the skin. The number and amplitude of folds is directly related to the density of the skin. Skin profile can be evaluated by determining the profile of the skin that received the density score by a trained professional.

  Furthermore, the effect on the reconstruction of the extracellular matrix by repeated application of the tensioning agent of the present invention to the skin can also be confirmed and / or evaluated in vivo by ultrasonic echography technology.

  Degradation and / or tissue breakdown of the extracellular matrix at the dermal papilla layer level is a major cause of skin aging. It is part of the cause of wrinkle appearance and a decrease in skin density, firmness and extensibility. This degradation and / or tissue breakdown of the extracellular matrix is even more apparent in people who are mature (> 40 years) or even more mature (> 60-65 years).

  Ultrasound ecography makes it possible to obtain 2D or 3D images of skin tissue. The intensity of the reflected echo provides information about the nature, density and tissue of the dermis components. In particular, the difference between the superficial dermis or dermal papilla layer and the deep dermis or reticulated dermis is demonstrated. This approach thus makes it possible to evaluate the effect on reorganization and reconstruction of the dermal papilla layer by repeated application of the tensioning agent of the present invention to the skin.

  The present invention will now be described with reference to the following examples, which are given for purposes of illustration and not limitation. In these examples, unless otherwise indicated, amounts are given in weight percent.

(Example)
(Example 1)
Demonstration of biological effects of tension agents
a) Effect on differential gene expression The biological effect of tension agents was demonstrated after application to Episkin® reconstructed epidermis.

Culture conditions for reconstructed epidermis The Episkin® reconstructed epidermis used was obtained on day 15. Reconstructed epidermis was kept in maintenance medium for 8 hours. The reconstructed epidermis was then transferred to DMEM / Ham F12 medium without EGF, pituitary extract and fetal bovine serum. The epidermis was kept in this medium for 24 hours to obtain equilibrium.

Tension agent: Preparation of ethyl methacrylate copolymer of methyl methacrylate / methacrylic acid copolymer type Step 1: Polymer synthesis 1 g Trigonox 21S (tert-butylperoxy-2-ethylhexanoate) and 200 g methyl ethyl ketone in a jacketed 21 reactor Put. The mixture was heated at reflux for 1 hour. After 1 hour, a mixture of 170 g methyl methacrylate and 30 g methacrylic acid was added dropwise over 1 hour. Viscosity appeared in the colorless mixture. Heating was interrupted 6 hours after the monomer addition.
NMR composition: methyl methacrylate 85.1%, methacrylic acid 14.9%
Mass by GPC, in THF (polystyrene standard): Mw = 98772; Mn = 61261; Mw = 105698 lp = 1.7

Step 2: Dispersion of polymer in water The above reaction mixture was mixed with 200 g of methyl ethyl ketone and heated to 60 ° C. 30.86 g 2-amino-2-methylpropanol and 1200 g water were added dropwise. The volatile solvent was evaporated by heating to 100 ° C. This gave a clear yellow aqueous dispersion.

  Then, 100 μL of the aqueous dispersion of the ethylenic copolymer was applied to Episkin in this medium and placed in a 40% relative humidity chamber temperature controlled at 37 degrees with contact with the epidermis for 24 hours. At the end of this period, the epidermis was removed and extracted for cDNA array testing.

Dedicated analysis using a minichip Gene expression analysis was performed using a standard DNA array containing 159 genes dedicated to this search and suitable for screening. These minichips were generated on nylon supports by immobilizing keratinocytes and marker-specific cDNAs that are typically involved in the regulation of skin physiology. Analysis is performed in an in-house optimized and miniaturized approach based on the use of mRNA and labeled phosphorus 33 (P33).

Schematically, cellular mRNA was extracted and purified using trireagent. The mRNA of each culture is “reversely” transcribed using deoxynucleotide triphosphates labeled with oligo dT and P33. Thus, a number of cDNA “target” labeled sequences were generated for each Episkin® reconstructed epidermis. These targets were then hybridized with an excess of cDNA “probes” immobilized on the membrane under optimized conditions. After washing, the amount of labeled target is visualized by autoradiography and phosphoimager direct counting. Membranes are analyzed with Imagequant software.
Results are expressed in relative expression units. The level of expression was calibrated with respect to 1) the average of background noise present in each membrane and 2) the difference in label intensity of the different probes used. This calibration is based on the difference in labeling intensity of the control gene. The average of the counts of “housekeeping gene” markers, whose expression is generally considered to be stable, was relatively considered as a control for quantifying the expression of other markers.
The limit of significance was set at 180% of the untreated control for the evoked effect and 50% of the control for the inhibitory effect.

Results Regulation of the expression of genes involved in keratinocyte differentiation:
Of the 159 genes present on the dedicated minichip, 25 genes were regulated by tension agents. These genes mediate regulation of keratinocyte and / or fibroblast physiology.

  The table below shows all the results obtained for the effect of tensioning agents on the expression of these genes.

  In particular, the tested ethylenic copolymers reduce the expression of several proteins that make up the stratum corneum, for example, corneodesmosine and loricrin, halved, supravacine, 1/3, etc. Suggesting that the copolymer attenuates the process of terminal differentiation. Acrylic copolymers further increase the expression of some of the cytoskeleton intermediate filament proteins, specifically cytokeratins found in fetal and regenerative epithelia. After 24 hours of treatment, cytokeratin 1 expression increases 10-fold and cytokeratin 19 expression increases 3-fold. These two cytokeratins have been described as being expressed in many types of epithelial tissues, particularly non-stratified and also fetal epithelium, despite being present in the adult epidermis (Haake et al., Exp Cell Res. Feb. 25, 1997; 231 (1) 83-95). Similarly, the expression of cytokeratin 2E / A is increased 10-fold: this cytokeratin 2 has been described as being expressed in both adult and fetal epidermis. Finally, cytokeratin 6 expression is increased 4-fold. This cytokeratin 6 has been described to be overexpressed in the regenerating epidermis, especially during the process of scar formation (Mazzalupo et al., February 2003; 226 (2): 356-65), This suggests that in the process of stretching provided by the application of the acrylic copolymer, the epidermis acquires regenerative epidermal features. The ethylenic copolymers of the present invention reduce the expression of complexes required for the process of keratinocyte differentiation, such as SPRL, also called LEP10, by 1/5, in the case of SPRL6 by 1/2.

  At the same time, these results indicate that the copolymer increases the expression of CRBP1 involved in the response of cells to retinol by a factor of 3, suggesting that stretch can increase the sensitivity of cells to retinol. Yes.

Regulation of TGFb expression
TGFb expression is increased 4-fold. This cytokine increases the expression and organization of all fibrillar collagen and type I plasminogen activator, PAI1, and decreases the expression of metalloproteinases, enzymes involved in the degradation of some extracellular matrix Let

  In the process of stretching provided by acrylic latex, the induced TGFb diffuses to the dermis level, thus allowing tissue repair to be induced. Increased expression of TGFb by stretching may be considered proof that the acrylic latex tensioning agent has increased the sensitivity of the cells to stretching.

Reduced expression of metalloproteinases Ethylenic copolymers reduce the expression of metalloproteinase 3, which is on the one hand involved in cell migration and on the other hand involved in the degradation of the extracellular matrix. Therefore, the ethylenic copolymer suppresses the degradation of the extracellular matrix and plays a part in cell migration.

Reduction of zyxin Ethylene copolymers reduce the expression of zyxin, which is located at the level of the adhesion complex and is known to be responsible for one end of cell morphology.

Increased cellular response to environmental stress Ethylenic copolymers increase the expression of the chaperone protein HSP90A by a factor of 10. HSP90A protein plays an important role in the process of protein maturation. HSP90A protein regulates the conformation of kinases or transcription factors and consequently controls its activity and degradation.

  Overall, these data indicate that mechanical stretch applied via an effective amount of the tensioning agent of the present invention is perceived by keratinocytes as a stimulus that results in a slowing of the process of epidermal differentiation; Regulation of gene expression described above further appears to indicate that the epidermis acquires a regenerative epidermal phenotype. These results show that topical application of an effective amount of at least one tensioning agent, or improves skin homeostasis, thus increasing skin thickness and / or improving skin mechanical properties, and / or It shows that it is possible to improve the brightness of the complexion. Furthermore, the increased expression of HSP90 suggests that stretching will enhance the ability of the epidermis to counter changes in skin homeostasis induced by environmental stress.

(Example 2)
Demonstration of effect of tensioning agent on complexion shine Prepare a serum containing the ethylenic copolymer described in Example 1;
A-water 50.45g
Ammonium polyacryl dimethyl tauramide
(Hostsacerine AMPS) 2.00g
Preservative 0.85g
B-Ethylene copolymer as described in Example 1
(7% dispersion in water) 46.70g

  The lightening and homogenizing effect of this serum and the cosmetic aspect as well were evaluated on a panel of 6 subjects with normal / mixed skin. After applying this serum at night for a month, a less complex face color was observed.

  These results show the biomechanical effect provided by topical application of tension agents to the skin. This effect is manifested by a decrease in epidermal differentiation and / or an increase in the regenerative power of the epidermis, allowing an improvement in the appearance of the skin, in particular the complexion.

(Example 3)
Tension Agent Mechanical Strength Test The mechanical strength test consists essentially of applying compressive stress to the point of failure of the tension agent to be tested on the surface of the flexible deformable foam. The use of this foam support makes it possible to quantify the substantial deformation that the tensioning agent applied to the surface undergoes under the test and thus the breaking strength of the tensioning agent.

  The substrate is composed of 13 mm thick neoprene foam.

  In the range of 25 ° C to 50 ° C at the highest weight concentration that forms a medium-appearance medium in water at a concentration of 7% in water or in the range of 25 ° C to 50 ° C, or observable with the naked eye At this temperature, a tensioning agent that is soluble or dispersible in water is deposited on the substrate, and after 24 hours drying, a 15-30 μm thick deposit is obtained. The adhesion was produced using a film stretching apparatus using a 650 μm wet film.

  The mechanical compressive stress is given by a cylindrical punch having a diameter of 1 mm, and the displacement rate of the punch is 0.1 mm / second.

  The test is performed using a TA-XT2i texture analyzer sold by Stable Micro System.

As a result, a curve of force F (unit N) is obtained as a function of displacement d (unit mm), and from this curve, the break point of the substance (tension agent) and the curve F = f at the _break point F _break (N) It is possible to determine the fracture energy W _break (J / m ² ) corresponding to the lower area of (d).

  All of the results obtained are shown below:

In particular, the mosaic effect tensioning agent of the present invention advantageously has a fracture energy between 0 and 20 J / m ² (preferably equal to 0) and a fracture deformation between 0 and 0.2 mm in this mechanical strength test. To form an adhesion characterized by

(Example 4)
Demonstration of the effect of tension agents on extracellular matrix reorganization Test principle To determine whether application of tension agents to the stratum corneum can induce improved extracellular matrix reorganization, 100 μl Each of the tensioning agents, Hybridur 875 sold by Air Products (at 15% by weight in water) and acrylic tensioning agent (the ethylenic copolymer prepared in Example 1, at 7% by weight in water), was added to Episkin®. ) Applied to reconstructed skin model.

  A reconstructed skin model composed of human keratinocytes attached to a support, often the dermal equivalent, and cultured under conditions that ultimately enter the differentiation program leading to the formation of the epidermal equivalent is Asselineau It can be prepared based on the protocol described in et al. (1987 Models in dermato., vol. III, Ed. Lowe & Maibach, pp. 1-7).

  Hybridur 875 sold by Air Products is prepared based on the description of US Pat. No. 5,977,215 and US Pat. No. 5,521,246.

  The effects of these tensioning agents on the dermis are observed 2 hours, 24 hours and 48 hours after application.

  Analysis is performed by two complementary imaging methods: optical microscopy (multiphoton and optical microscopy with transmission through semi-thin sections) and electron microscopy (scanning electron microscopy).

  Multiphoton microscopy allows for rapid identification, on any time scale, of active ingredients that would be active in the extracellular matrix without prior sample preparation.

  With its three-dimensional resolution, it is possible to determine the depth at which mechanical stimulation will result in dermal improvement.

  During this initial observation, the sample is analyzed by a scanning electron microscope, which allows a higher degree of resolution and thus allows the collagen fibrils to be individualized.

  The improvement observed in the extracellular matrix is associated with an improvement at the fibroblast level by examination with light microscopy through semi-thin sections.

Results Electron and photon microscopy observations showed that the dermal collagen fibrils were reorganized 48 hours after application of the tested tension agent, as shown in Figure 3, and also the length and number of fibroblasts increased. It also shows that it induces.

  The extracellular matrix collagen fibrils are associated to form a larger density network in the fibril structure. This new tissue is associated with the synthesis of proteoglycans, such as decorin or other lumicans that are known to undergo association with several collagen molecules and thus regroup into a well-ordered network. It seems that there is.

  Thus, the mechanical stress induced by the tension agent stimulates the fibroblasts, resulting in reorganization of their cytoskeleton, and thus this is very short-term, as was 48 hours after application. It is dynamic.

It is a figure of the example (magnification x30) of mosaic-like adhesion of Hybridur 875. FIG. 6 is a diagram of a force curve as a function of displacement. It is a conceptual diagram of the electron micrograph which shows the effect with respect to the reorganization of the collagen fiber of the extracellular matrix of Hybridur 875.

Claims (37)

  Cosmetic use of a composition comprising at least one mosaic effect tensioning agent to increase skin thickness in a physiologically acceptable medium.   Cosmetic use of a composition comprising at least one mosaic effect tensioning agent to increase the thickness of the epidermis in a physiologically acceptable medium.   Cosmetic use of a composition comprising in a physiologically acceptable medium at least one mosaic effect tensioning agent for improving the brightness of the complexion.   Cosmetic use of a composition comprising at least one mosaic effect tensioning agent to improve skin density in a physiologically acceptable medium.   Cosmetic use of a composition comprising in a physiologically acceptable medium at least one mosaic effect tensioning agent for promoting the regeneration and / or reconstitution of the nipple dermis.   Cosmetic use of an effective amount of at least one mosaic effect tensioning agent as an agent intended to increase skin thickness in a composition for topical application of skin comprising a physiologically acceptable medium.   Cosmetic use of an effective amount of at least one mosaic effect tensioning agent as an agent intended to increase the thickness of the epidermis in a composition for topical application of the skin comprising a physiologically acceptable medium.   Cosmetic use of an effective amount of at least one mosaic effect tensioning agent as an agent intended to improve facial brightness in a composition for topical application of the skin comprising a physiologically acceptable medium.   Cosmetic use of an effective amount of at least one mosaic effect tensioning agent as an agent intended to improve skin density in a composition for topical application of skin comprising a physiologically acceptable medium.   Cosmetic of an effective amount of at least one mosaic effect tension agent as an agent intended to promote the regeneration and / or reconstitution of the nipple dermis in a composition for topical application of the skin comprising a physiologically acceptable medium use.   Beauty of an effective amount of at least one mosaic effect tension agent as an agent intended to promote extracellular matrix regeneration and / or reconstitution in a composition for topical application of skin comprising a physiologically acceptable medium Use.   At least one effective amount as an agent intended to enhance and / or improve skin elasticity and / or firmness and / or tension in a composition for topical application of skin comprising a physiologically acceptable medium. Cosmetic use of two mosaic effect tension agents.   An effective amount of an agent intended to reduce the process of epithelial differentiation and / or promote skin regeneration and / or renewal in a composition for topical application of skin comprising a physiologically acceptable medium Cosmetic use of at least one mosaic effect tension agent.   The cosmetic according to any one of claims 1 to 13, characterized in that the mosaic effect tensioning agent is selected from (i) mineral tensioning agents, (ii) tensioning polymers, and mixtures thereof. use.   15. The effect of a mosaic effect tensioning agent on the skin thickness and / or complexion brightness and / or skin mechanical properties is a continuous biological effect. Cosmetic use according to any one of the above.   As an agent intended to regulate the expression of genes involved in skin homeostasis through the propagation of mechanical tension, including mechanoceptor activation, in compositions for topical application of skin containing a physiologically acceptable medium Cosmetic use of an effective amount of at least one mosaic effect tension agent.   The cosmetic effect according to any one of the preceding claims, characterized in that the mosaic effect tensioning agent is a mineral tensioning agent selected from mixed silicates, colloidal particles of inorganic fillers, and mixtures thereof. use.   Cosmetic use according to claim 17, characterized in that the colloidal particles of the inorganic filler are selected from colloidal silica.   Cosmetic use according to any one of the preceding claims, characterized in that the mosaic effect tensioning agent is a synthetic polymer.   Said synthetic polymer comprises (a) 70 wt% to 90 wt% copolymer of at least one alkyl acrylate and / or at least one alkyl methacrylate and / or styrene and (b) 10 wt% copolymer of at least one ionic hydrophilic monomer. 20. Composition according to claim 19, characterized in that it is selected from acrylic copolymers composed of% to 30% by weight.   20. A composition according to claim 19, characterized in that the synthetic polymer is an ethylenic copolymer.   20. Composition according to claim 19, characterized in that the synthetic polymer is an interpenetrating polymer network type polymer.   24. The composition of claim 22, wherein the interpenetrating polymer network comprises a polyurethane polymer and an acrylic polymer.   Cosmetic use of a composition comprising in a physiologically acceptable medium at least one interpenetrating polymer network for enhancing and / or improving skin elasticity and / or firmness and / or tension.   Cosmetic use of a composition comprising at least one interpenetrating polymer network to promote extracellular matrix regeneration and / or reconstitution in a physiologically acceptable medium.   Cosmetic use of a composition comprising at least one interpenetrating polymer network to promote skin regeneration and / or renewal in a physiologically acceptable medium.   Cosmetic use according to any one of claims 24 to 26, characterized in that the interpenetrating polymer network comprises a polyurethane polymer and an acrylic polymer.   28. The mosaic effect tensioning agent is present in the composition in an amount ranging from 1 to 30% by weight of active ingredient relative to the total weight of the composition. Cosmetic use according to item.   29. The mosaic effect tensioning agent is present in the composition in an amount ranging from 2 to 30% by weight of active ingredient relative to the total weight of the composition. Cosmetic use according to item.   30. The mosaic effect tensioning agent is present in the composition in an amount ranging from 3 to 20% by weight of active ingredient relative to the total weight of the composition. Cosmetic use according to item.   Dull, characterized in that a composition comprising an effective amount of at least one mosaic effect tensioning agent in a physiologically acceptable medium is applied to a person with a dull and / or poorly defined complexion A cosmetic treatment method for complexion that is not well defined and / or well defined.   A composition comprising an effective amount of at least one mosaic effect tensioning agent in a physiologically acceptable medium, a person with soft and / or sagging skin, or an area of the body that has lost elasticity and / or stiffness A cosmetic treatment method for soft and / or sagging skin, characterized in that it is applied to a skin.   A skin cosmetic treatment method comprising applying to the skin at least twice a week a composition comprising 3% by weight of at least one mosaic effect tensioning agent, based on the total weight of the composition.   34. A cosmetic method according to claim 33, wherein the composition is applied to the skin at a frequency of at least once a day.   35. A cosmetic method according to any one of claims 31 to 34, wherein the composition is applied to the skin of the face and / or neck.   35. A cosmetic method according to any one of claims 31 to 34, wherein the composition is applied to the skin of the body.   The cosmetic method according to claim 36, wherein the composition is applied to the skin of the abdomen and / or thigh.

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