Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q19/00—Preparations for care of the skin
  • A61Q19/08—Anti-ageing preparations
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/60—Sugars; Derivatives thereof
  • A61K8/602—Glycosides, e.g. rutin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q19/00—Preparations for care of the skin

Definitions

• the present invention relates to a new use of galactosylglycerides, very particularly digalactosyldiglycerides, and extracts of natural origin containing these products, in the cosmetic, pharmaceutical and in particular dermatological fields.
• the invention relates to a new use of galactosylglycerides as agents intended to intensify the production of extracellular fibronectin.
• This new use finds its application in particular in cosmetics or dermatology, in particular for the preparation of compositions intended for firming the skin, accelerating healing, preventing or treating wrinkles, and, in general, preventing or treat the effects of skin aging.
• fibronectin exists in two forms: a soluble form found in plasma and other body fluids, and an insoluble matrix form distributed in loose connective tissue and various basement membranes. Fibronectins are high molecular weight glycoproteins (450,000) formed from two similar subunits. DNA séquen ⁇ age c studies have shown that plasma fibronectin and cell came from a single gene by alternative splicing of the first transcribed.
• the carbohydrate part of the molecule varies according to the fibronectins - the constituent oses are sialic acid, hexoses, hexosamines - the oligossacharidic chains are asymmetrically distributed on the molecule with highly glycosylated domains and others devoid of carbohydrates.
• Fibronectins have common immunological characteristics vis-à-vis polyclonal antibodies. In addition, they interact with collagens, fibrin, proteoglycans, certain elements of the cytoskeleton, bacteria, cell surfaces (fibronectin and its role in cell-matrix interactions. J. LABAT-Robert, review biology society 1986, 180, p. 142-150).
• Fibronectin has a complex molecular structure consisting of multiple specific binding sites and it appears that the complex biological phenomena in which "fibronectins" are involved are related to their structures (fibronectins: multifunctional modular glycoproteins, Richard O hynes and Kenneth M. Yamada - The Journal of Cell Biology 1982, 95: 369-377) for example, morphology, cytoskeleton organization, oncogenic transformation, phagocytosis. In the central area of the "fibronectin” molecule is the binding site with cell surfaces.
• fibronectin As the prototype of the protein responsible for the adhesion of cells to their substrate, but the expression of fibronectin and its receptors regulate several cellular properties: polarity, capacity to migrate, the state of differentiation (fibronectin and its receptors E.Ruoslahti, Ann. Rev. Biochem. 1988, 57: 375-413).
• the fibronectin subunits have sites of interactions with receptors of the cell membrane, the integrins which recognize the RGD peptide.
• the integrins which recognize the RGD peptide.
• galactolipids are among the essential constituents of living things, both animals and plants. In higher beings, they are present throughout the body, mainly as constituents of cell membranes. In plants, they are in particular localized in the chloroplastic envelope. Many publications are devoted to them, such as the following publications:
• the galactolipids include in particular the galactosylglycerides.
• the latter are well known, and can be extracted from plants, for example from cereals.
• DGDG digalactosyldiglycerides
• JP-A2-0503750 which describes the use of the same products to improve the quality of products made from wheat flour
• the invention relates to the use of galactosylglycerides, very particularly digalactosyldiglycerides, and in particular plant extracts containing these products, for all cosmetic or pharmaceutical, in particular dermatological, applications where it is sought to obtain a densification of the network. extracellular fibronectin.
• the main object of the present invention is therefore to solve the technical problem of providing a cosmetic or pharmaceutical composition, in particular a dermatological composition, having excellent efficacy in preventing or treating the effects of skin aging, in particular the appearance of wrinkles. and on skin firming.
• the invention relates to the use of at least one galactosyl-diglyceride or of an extract of natural origin containing it as a cosmetic agent promoting the formation of extracellular fibronectin by fibroblasts, thus making it possible to improve cutaneous healing, to strengthen the biomechanical properties of the dermis or connective tissues, to improve the appearance of the surface of the skin, and making it possible, in particular, to prevent or treat the effects of skin aging, such as wrinkles or sagging tissues skin support.
• the invention therefore relates, according to one of its essential characteristics, to the use of at least one galactosylglyceride or of an original extract natural containing it as a cosmetic agent making it possible to improve skin healing, to strengthen the biomechanical properties of the dermis, to improve the appearance of the skin surface, or to prevent or treat the effects of skin aging, such as wrinkles or sagging skin support tissue.
• improvement of the biomechanical properties of the dermis is meant any improvement of biological origin of the structural quality of the dermis.
• the intensification of the extracellular fibronectin network makes it possible to improve the adhesion of cells to intercellular macromolecules, such as collagen.
• the use according to the invention more particularly makes it possible to obtain skin firming, prevention of the appearance of wrinkles or attenuation of their depth.
• the above-mentioned extract of natural origin is a plant extract, in particular a cereal extract such as wheat or oats, or an extract of leaves or nuts of Ginkgo Biloba.
• the galactosylglycerides which are useful according to the invention are very particularly the monogalactosylmonoglycerides (MGMG), the monogalactosyldiglycerides (MGDG), the digalactosylmonoglyc ⁇ rides (DGMG) and the digalactosyldiglycerides (DGDG).
• MGMG monogalactosylmonoglycerides
• MGDG monogalactosyldiglycerides
• DGMG digalactosylmonoglyc ⁇ rides
• DGDG digalactosyldiglycerides
• the mono- or digalactosyldiglycerides will be chosen.
• the galactosylglyceride will correspond to formula (I):
• Gai represents a galactopyranosyl group, preferably beta-D-galactopyranosyl,
• - Ri represents an acyl group of formula
• R represents an aliphatic hydrocarbon chain, saturated or not, preferably linear, and comprising from 9 to 29 carbon atoms
• - R2 represents a hydrogen atom or an acyl group, identical or different from R ⁇ , of formula
• a chain consisting of a chain of several sugars, preferably two or three sugars, chosen from the group consisting of alpha- and beta-D- galactopyranosyle, alpha-D-glucopyranosyle, alpha- D- and alpha-L- manopyranosyle.
• the galactosyl ⁇ glycerides are chosen from mono- and digalactosyldiglycerides (respectively MGDG and DGDG) of formula (I) above, in which
• Rj and R2 correspond to the definition given above, except that R2 necessarily represents an acyl group
• - A represents a single bond or an alpha- or beta-D- galactopyranosyl group.
• the galactosyldiglyceride above is chosen from digalactosyldiglycerides (DGDG), that is to say from products in which A represents an alpha- or beta-D-galactopyranosyl group.
• DGDG digalactosyldiglycerides
• galactosylglycerides will be chosen for each of the preceding variants for which: - R ⁇ represents an acyl group of formula
• R represents a linear aliphatic hydrocarbon chain containing 15, 17 or 19 carbon atoms, saturated or comprising from 1 to 5 double bonds, in position 7, 10 and / or 13 for an acyl group of 16 carbon atoms, in position 9, 12 and / or 15 for an acyl group of 18 carbon atoms, and in positions 5, 8, 10, 14 and / or 17 for an acyl group of 20 carbon atoms.
• - R2 represents a hydrogen atom or an acyl group, identical or different from R ⁇ , of formula
• the invention also relates to a cosmetic treatment process intended in particular to reinforce the biomechanical properties of the dermis by an intensification of the formation of extracellular fibronectin by fibroblasts, to obtain a skin tightening or the improvement of the surface of the skin or to prevent or treat the effects of skin aging such as the appearance of wrinkles, consisting in applying locally to the areas of the skin to be treated a composition containing at least one galactosylglyceride or a plant extract containing it.
• the galactosylglyceride will advantageously be chosen from the galactosylglycerides of formula (I) described above, the preferred products constituting the same subclasses as those defined above.
• the extracts of natural origin containing the galactosylglycerides which can be used for the implementation of the invention, can be obtained by extraction methods well known to those skilled in the art.
• the extraction solvent used will preferably be a polar solvent, such as an alcohol, an ether or a halogenated hydrocarbon. We will choose for example methanol, ethanol, isopropanol, ethyl ether or chloroform.
• the same galactosylglycerides and very particularly the digalactosyldiglycerides, and the natural extracts containing them can be used as active agent of pharmaceutical compositions, in particular dermatological compositions, intended to intensify the synthesis of extracellular fibronectin.
• the invention relates to the use, as active principle, of at least one galactosylglyceride or of an extract of natural origin containing it, for the preparation of a pharmaceutical composition, in particular dermatological, intended to prevent or treat various pathologies accompanied by a deficiency in the intensity of the extracellular fibronectin network in the connective tissues, in particular in the dermis, in improving the biomechanical properties of the skin, in preventing or treating the effects of aging, in particular of skin aging, to promote healing or to obtain skin firming.
• the invention relates very particularly to the use, as active principle, of at least one galactosylglyceride, as described above, in particular a digalactosyldiglyceride, for the preparation of compositions for the abovementioned indications.
• the galactosylglycerides are advantageously chosen for this application from family I defined above and the sub-families of preferred products are the same as those defined above.
• the abovementioned active principle is an extract of natural, animal or plant origin, as previously defined.
• it will be a plant extract, in particular a cereal extract, such as wheat or oats, or an extract of Gingko Biloba leaves or nuts.
• compositions according to the invention are therefore very particularly intended for firming the skin, accelerating or improving the healing process, preventing the appearance of wrinkles or their treatment, and a generally for the prevention or treatment of the effects of skin aging.
• the compositions of the invention can therefore, in particular, be advantageously used to reduce the depth of wrinkles, in particular those of the face and the neck.
• the galactosylglyceride concentrations of between 0.001 and 10% by weight relative to the total weight of the composition containing it will preferably be used. This concentration will preferably be between 0.01 and 5% by weight relative to the total weight of said composition.
• Plant extracts containing at least one galactosylglyceride in particular cereal extracts such as wheat or oats, will be used in a particularly advantageous manner.
• Such products exist commercially.
• commercial products mention may be made of commercial products containing DGDG and MGDG available from SIGMA Chemical Company (Saint-Louis, Mo, USA).
• the administration of galactosylglycerides is carried out according to conventional methods, allowing stimulation of the production of extracellular fibronectin.
• the simplest route of administration is the topical route, in particular when one seeks to restore or reinforce the biomechanical properties of the cutaneous support tissues to firm the skin, or to prevent or attenuate the appearance of wrinkles, especially those of the face or neck.
• compositions according to the invention will be formulated, in accordance with techniques well known to those skilled in the art, suitably for topical administration, for example in the form of a cream, milk, lotion, gelled or not. , or ointment.
• the galactosylglyceride or the extract containing it is incorporated into an excipient, vehicle or carrier cosmetically or pharmaceutically, in particular dermatologically acceptable.
• Such supports are well known to those skilled in the art and also result from examples of cosmetic compositions or pharmaceutical compositions, in particular dermatological compositions described below which are general in scope.
• FIGS. 1 to 4 which are an integral part of Example 1, are copies of photographs obtained during observation under a fluorescent microscope of the extracellular network of fibronectin secreted respectively by:
• the immunolocalization of fibronectin is based on the general principle of the specific binding of an antibody to its antigen.
• the technique is performed by indirect immunostaining. First, an anti-fibronectin antibody prepared in rabbits is brought into contact with the cell layer.
• the complex formed by the binding of the specific antibody to its antigen is revealed by the addition of a globulin directed against rabbit Ig G coupled to a fluorochrome, here, R phycoerythrin.
• the antibodies used are:
• Goat antibody F (ab ') 2 rabbit anti-immunoglobulin (G + L) labeled with phycoerythrin (TAGO Ref. 4920).
• the cells used are fibroblasts from mammary or abdominal surgical plasties from healthy adult donors.
• the cells are inoculated on glass slides, and 24 h after inoculation, the medium is renewed in the presence or not of DGDG.
• the initial culture medium is MEM + 10% fetal calf serum (SVF).
• the medium consists of MEM medium + 2.5% fetal calf serum.
• the DGDG is dissolved in DMSO and used on the cultures at the final concentration of 750 ⁇ g / ml. Cultivation operations take place as follows:
• the cells After rinsing the coverslips with PBS buffer, the cells are fixed for 20 min with paraformaldehyde (3.7% in PBS) at 4 ° C.
• the anti-fibronectin antibody (diluted to 1 / 250th in PAB) is brought into contact with the cells. for 60 min at 4 * C.
• This operation is followed by passing through a buffer solution (PAB) and then 2 baths of 15 min in the same buffer.
• PAB buffer solution
• the second part of the reaction is carried out by adding the fluorescent conjugate (diluted to 1 / 500th in PAB) for 45 min at room temperature. The cells are then again rinsed with PBS.
• Each strip is then dried and mounted on a slide (mounting medium: 33% glycerol in PBS).
• the orientation of the fibers is clear.
• the condensation of the fibers present in certain cells contrasts with the presence of fine fibers interspersed and isolated.
• the fibers are associated with each other, intertwined. They mark a kind of swirls, the outline of the cells is not discernible
• the fibers appear to be nested in a net with relatively tight stitches, of the "lace” or "skein” type.
• DGDG causes a considerable increase in the formation of extracellular fibronectin by fibroblasts, regardless of the age of the subjects.
• Example 2 Demonstration of the activity of digalactosyldiglyceride increasing the adhesion capacity of fibroblasts.
• the purpose of this experiment is to verify the stimulation of the adhesion capacity of normal human fibroblasts treated with DGDG. For this, we will observe the speed of adhesion to a plastic support of these cells in culture.
• a culture of normal human fibroblasts is obtained in a 75 ml flask, obtained as indicated above in Example 1. These cells are cultured in a conventional manner in MEM medium supplemented with 10% fetal calf serum, to which is added DGDG (SIGMA) at the concentration of 750 ⁇ g / ml. The culture is carried out for one week, with two replenishments of the culture medium in the week, always with the same concentration of DGDG.
• SIGMA DGDG
• the cells are peeled off, leaving a 2 mM solution of EDTA (ethylenediaminetetraacetic acid) to act for 30 minutes.
• EDTA ethylenediaminetetraacetic acid
• the cells After centrifugation, the cells are resuspended in a conventional culture medium (MEM supplemented with 10% fetal calf serum).
• MEM fetal calf serum
• a stable dispersion is prepared containing 1% by weight of DGDG and 2% of collagen.
• the dispersion is gelled by adding 0.2% by weight of Carbopol 940 and a preservative is added.
• Example 4 Product with Anti-Wrinkle Effect A stable emulsion is prepared containing:
• 80% water + classic preservatives as follows: The DGDG is dissolved in the oil and the whole is brought to 75 ° C. The water with the preservatives is heated separately to 75 # C. Part of the water is then incorporated into the fatty phase, then the whole is introduced into the remaining part of the aqueous phase, at 75 ° C. with magnetic stirring. The emulsion is brought to 80 ° C. still under magnetic stirring, then homogenized for 5 min at 11,000 rpm, using Ultra - Turax. It is then immersed in an ice bath in order to obtain rapid cooling, freezing the structure.

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• 1995
  • 1995-02-15 FR FR9501714A patent/FR2730409B1/fr not_active Expired - Fee Related
• 1996
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