FR2871381A1 - Topical cosmetic/dermatological composition, useful e.g. to fight against signs of cutaneous ageing, comprises an marsh mallow extract (Althea officinalis) - Google Patents

Abstract

Topical cosmetic and/or dermatological composition (I) to fight against signs of cutaneous ageing, comprising an extract of marsh mallow (Althea officinalis) (A), is new. An independent claim is also included for a cosmetic process to fight against the signs of skin ageing, comprising applying (I) on the affected skin zones. ACTIVITY : Dermatological. No biological data is given. MECHANISM OF ACTION : Facial muscular contraction inhibitor.

Description

2871381 1

  The present invention relates to a new cosmetic and / or dermatological composition intended to prevent and treat the signs of cutaneous aging, and more particularly to a composition based on marshmallow extract (Althea officinalis) having a relaxing effect on the skin, useful against facial muscle contractions responsible especially for expression lines.

  The skin is a real organ comprising several integrated layers, ranging from the superficial layer, the epidermis, to the deeper layers, the dermis and the hypodermis, and each has specific properties allowing the whole to react. and adapt to the conditions of his environment.

  The epidermis, composed mainly of keratinocytes (90% of epidermal cells), melanocytes (2 to 3% of epidermal cells) and Langerhans cells, has a variable thickness depending on the different parts of the body. Since it constitutes the outer layer of the skin, the epidermis plays a fundamental role in ensuring the protection and maintenance of good trophicity. This is why many compositions have been developed to protect and improve its functions, including strengthening its elasticity and firmness.

  The dermis, thicker, solid, rich in nerves, blood vessels and sweat glands, consists mainly of collagen, elastin and proteoglycans. These three types of molecules are synthesized by dermal fibroblasts. Collagen fibers, which account for 70% of the dry weight of the dermis, provide the mechanical strength and texture of the skin, elastin is responsible for elasticity, and proteoglycans play a major role in the structure and hydration of the skin. the skin. Other cells such as macrophages and leucocytes are also present in the dermis layer.

  B1501en 2871381 2 The hypodermis, which is the deepest layer of the skin, contains lipid-producing fat cells so that the subcutaneous tissue makes a fat layer that protects muscles, bones, and internal organs from shock.

  The aging of the skin can be intrinsic, or extrinsic that is to say caused by the environment.

  One of the first signs of skin aging is a loss of elasticity and the formation of fine lines and wrinkles, which are a direct result of the deterioration of the dermis layer of support. The appearance of pigment marks, the decrease in the thickness of the skin and its collapse are also changes observed during aging.

  Many factors contribute to accelerate the breakdown of collagen dermis, and especially sun exposure, free radicals, some hormonal changes associated with old age and tobacco.

  The first signs of skin aging, such as wrinkles and fine lines, are usually caused by stress and biological and physiological changes, accelerated by the external environment. In fact, the ability of the skin to replace damaged collagen decreases over time, and spaces and irregularities appear in the collagen network. At the skin level, aging causes in particular a decrease in protein synthesis (collagen, elastin), a decrease in the synthesis of proteoglycans among others, as well as an increase in MMP3 type metalloproteinases.

  This aging of the skin is accompanied by feelings of heaviness, pressure during sleep and also contraction of the facial muscles, determining expression lines, especially around the eyes and mouth, or the modification of epidermal microrelief due to especially stress. In particular, the expression wrinkles are caused by multiple contractions and twitches that the facial features undergo daily under the action of subcutaneous facial muscles that contract and relapse successively incessantly according to the rhythm of the emotions.

  To combat these signs of aging, it is therefore necessary to reduce the contraction forces of the facial muscles by exerting an inhibition of the release of neuromediators. This phenomenon of inhibition has the effect of causing a relaxation of facial features and reduce the depth of facial wrinkles.

  Certain treatments are known which may have the effect of limiting or inhibiting facial muscle contractions. Thus, it is known that it is possible to perform a cosmetic treatment by injection of botulinum toxin in the wrinkles in order to freeze the cells in contact with the toxin, giving the skin a smoother appearance. Some cosmetic compositions contain exfoliating substances such as alpha-hydroxy acids, for example lactic acid and glycolic acid, facilitating the removal of dead cells and stimulating the formation of collagen and elastin. US Pat. No. 5,925,348 describes a cosmetic composition comprising a sacred lotus seed extract as a source of methyl transferase intended to combat cutaneous aging. Retinoic acid or retinol-based compositions are also known which can act against the signs of skin aging such as dryness, loss of elasticity of the skin and the formation of wrinkles, as well as skin-conditioning creams. magnesium or manganese inhibiting the flow of calcium in the cells, causing muscle contraction, to reduce microcrispations of the skin and slow down the appearance of expression lines.

  However, there is still a need for novel alternative topical compositions for effectively controlling the effects of cutaneous aging, including topical compositions based on suitable plant extracts derived more particularly from plants known for their use. favorable properties.

  Marshmallow (Althea officinalis) is a plant whose parts, such as leaves and especially roots, have been used for a long time, in particular in food compositions or dietary supplements, but also because of known properties. Thus, it has been observed that the marshmallow root has an anti-inflammatory and calming effect on the body and also an anti-tussive effect which justified its use in pediatric syrups. It is known that the marshmallow root contains a neutral sugar, rhamnogalacturonan, which inhibits reflex cough caused by a mechanical stimulus in the cat at a dose of 50 mg / kg of weight (G. Nosalova et al., Pharmazie, 1992). , 47 (3): 224-6). Marshmallow root has also been used for a long time as a masticatory to calm the effects of dental flares in children.

  Extracts of flowers or marshmallow leaves have also been proposed in phytopharmaceutical compositions intended to promote the hydration of the skin, or as analgesics for the treatment of diseases of the oral cavity and the larynx.

  Its use as an additive in food or confectionery compositions is also well known. Thus US Pat. No. 6,605,306 describes a dietary supplement containing various plant extracts including Althea officinalis for its anti-inflammatory action.

  According to the present invention, it has been found that it is possible to act effectively against the facial muscular contractions responsible for the signs of cutaneous aging and in particular the expression lines, by using topical compositions based on extracts of marshmallow (Althea officinales).

  The subject of the present invention is therefore a new cosmetic and / or dermatological composition based on plants, 2871381 5 and more particularly based on marshmallow extract (Althea officinalis) having effects of inhibition of uncontrolled facial muscle contractions. origin of expression lines.

  The subject of the present invention is also the use of a marshmallow extract (Althea officinalis) for the preparation of a topical composition intended to combat the signs of cutaneous aging, and in particular expression lines caused by contractions. uncontrolled facial muscles.

  The subject of the present invention is also a cosmetic process for combating the signs of aging of the skin, and more particularly expression wrinkles resulting from facial muscle contractions, consisting in applying to the areas of the skin affected a topical composition containing a quantity effective marshmallow extract (Althea officinalis) according to the present invention.

  The invention also relates to the use of a marshmallow extract (Althea officinalis) for the preparation of a dermatological drug for the prevention and treatment of uncontrolled facial muscular contractions.

  The compositions according to the present invention are distinguished in that they comprise a marshmallow extract (Althea officinalis) in an amount effective for combating the signs of cutaneous aging, and more particularly expression lines, as well as carriers and excipients. acceptable in dermatology and cosmetology.

  Thus, the topical compositions of the invention may be advantageously used in dermatology and cosmetology for the treatment or prevention of damage related to aging of the skin, and more particularly to prevent or reduce expression lines resulting from contractions. uncontrolled facial muscles.

  The marshmallow extracts used in the compositions according to the present invention are preferably in aqueous form.

  According to an advantageous embodiment, the extract that can be used in the invention is obtained by leaching from pulverized marshmallow roots (Althea officinalis).

  The extract is in the form of an amber-yellow liquid with a characteristic odor, characterized by: - dry matter 1.5 to 2% - water 98 to 98.5% - density 0.993 to 1.00 - refractive index 1.336 - pH 6.0 to 6.2 - neutral oses 839 mg / L - acidic oses 459.8 mg / L The tests carried out by the Applicant showed that among the various parts of the plant it is better to use the root, which is readily available and whose conservation is generally not a problem.

  The marshmallow extracts of the compositions according to the present invention have shown, in in vitro tests, inhibition effects of neurotransmitters capable of generating reflex muscular contractions, thanks to neuropeptides the modulation of which is linked to the production of acetyl choline and 'adrenaline. The tests were performed on a dorsal ganglion culture of mouse fetus.

  The results, detailed below, have shown, according to the concentrations used: a decrease of up to 26% of the substance P, a decrease of up to 30% of the CGRP (Calcitonin Gene Related Protein), A decrease of up to 21% in acetyl choline, a decrease of up to 30% in the affinity of the substance P receptor for human keratinocytes in culture. These results were obtained with an extract of marshmallow roots (Althea officinalis), and confirm that, in topical application, such an extract, or a composition containing it, has a muscular relaxation effect.

  The tests were carried out using samples respectively dosed at 0.1%, 0.5% and 1% of extract.

  The results are explained in the examples below.

  The marshmallow extract according to the present invention can be used alone or in combination with other compatible active principles that is to say not likely to react on each other or to mask or limit their respective effects.

  According to an advantageous embodiment, the marshmallow extract is supplemented with active ingredients or auxiliary ingredients chosen for their complementary properties, in order to reinforce the effect of inhibiting facial muscle contractions or to supplement the anti-aging effects of the composition.

  Thus it may be advantageous to combine marshmallow extract (Althea officinalis) with appropriate amounts of endorphin-producing substances, for example Calmosensine (acetyl dipeptide-1-cetyl ester), Bacopa monieri extracts, Boswelia serrata, mint piperata; amaranth seed protein (Amarantus caudatus) or pea globulins to obtain a skin tightening effect; Calophylum oil, an oil rich in A7 sterols such as Argan oil, an unsaturated oil rich in omega 3 and 6, or corn protein, to enhance the anti-wrinkle effect; Imperata cylindrica, for example MOIST 24 from Sederma, to promote hydration of the skin by modifying the osmotic pressure; Echium oil for its anti-inflammatory effect; or a palmitoyl pentapeptide-3 such as Matrixyl or derivatives such as palmitoyl GHK (having the glycyl-Histidyl-Lysine chain) and palmitoyl GQPR (Glycyl-Glutamyl-Prolyl-Arginine) or palmitoyl VGVAPG (Valyl) -Glycyl-Valyl-Alanyl-Prolyl-Glycine) combined with a ceramide-2, as well as in general any association with a ceramide.

  The compositions according to the present invention may be in any of the usual dosage forms suitable for topical application, and preferably in the form of lotion, serum, milk or cream.

  They may comprise between 0.2% and 10% by weight of marshmallow extract, as defined above, relative to the total weight of the composition, and preferably between 0.5 and 5% by weight. The choice of the dose in the composition can be made according to the intended use. For prolonged anti-wrinkle treatment, lower doses, in the form of milk or cream dosed at about 0.5 to 1%, are preferably used, whereas spot treatment may require higher doses, for example a serum dosed at 5 or 6%.

  The compositions in accordance with the present invention may be presented in the forms conventionally used for topical application, that is to say in the form of a lotion, gel, emulsion (in particular cream or milk), mask, ointment, liposomes or else transdermal patches, containing compatible and pharmaceutically acceptable excipients and common carriers. They may also be in the form of wipes soaked in a solution containing the marshmallow extract according to the invention. These forms of topical administration are prepared by the known techniques, and for example, in the case of a cream, by dispersion of a fatty phase in an aqueous phase to obtain an oil-in-water emulsion, or conversely to prepare a water-in-oil emulsion. In the case of creams, it is preferred to use lamellar structure emulsions containing little or no ethoxylated products.

  The topical compositions according to the invention may for example comprise suitable excipients for external topical administration, in particular dermatologically and cosmetologically acceptable excipients. These excipients suitable for the formulation are well known to those skilled in the art and include in particular penetration agents such as ethoxydiphenol, phytantriol, octyl dodecanol and escin; thickeners such as natural gums and synthetic polymers; emollients and surfactants such as cetearyl octanoate, isopropyl myristate, cetearyl isononanoate, dimethicone, cyclomethicone, polyglyceryl 3-diisostearate, hydrogenated polyisobutene, cetyl alcohol, cetyl palmitate cetyl phosphate; emulsifiers; preservatives such as phenoxyethanol, methyl parahydroxybenzoate (methylparaben), ethyl parahydroxybenzoate (ethylparaben), propylparaben parahydroxybenzoate (propylparaben) and Phenonip associating phenoxyethanol and methyl, ethyl, butyl and isobutyl parahydroxybenzoates; dyes; the perfumes; etc. Other ingredients may be used in the compositions: moisturizing agents such as propylene glycol, glycerol, butylene glycol and also antioxidant vitamins such as vitamin E, for example tocopherol acetate or tocotrienol, vitamin C, natural polyphenols. Skin conditioning agents such as nylon and boron nitride can also be added to the composition.

  The following examples further illustrate the invention without limiting its scope. In all of the following examples of compositions, parts are by weight unless otherwise indicated.

Example 1

  According to conventional techniques, a lightening lotion of the facial muscles having the following weight composition is prepared.

  Marshmallow Root Extract Tetrasodium EDTA Butylene Glycol Glycerin Phenoxyethanol Magnesium Aspartate Carbomer Tocopherol Self-Emulsifying Behenyl Alcohol Octyl Dodecanol Phenyl Dimethicone 1000 Decyl Caprylate Cetyl Palmitate Glycerol Monostearate Argan Oil Calophylum Oil Amaranth Protein Corn Protein Tromethamine Calmosensin Preservatives Essential oils Demineralised water The marshmallow root extract used in the above composition is an aqueous extract obtained by leaching cut and powdered roots of marshmallow (Althea officinalis) into a suitable percolator.

  The lotion having the composition indicated above is used in application on the face, once or twice a day.

  1.0 3.0 0.5 0.5 0.1 0.2 0.7 5.0 3.5 3.0 3.0 3.0 3.0 2.0 1 , 0 0.2 3.0 0.3 0.3 qs 100.0 2871381 11

Example 2

  A facial tissue lightening wipe is prepared with a lotion having the following weight composition.

  Marshmallow Root Extract 3.0 Glycerin 5.0 PEG 400 4.0 70% Sorbitol 2.0 Butylene Glycol 4.0 Phenonip 0.5 Water-soluble Fragrance 1.0 Demineralized Water qs 100.0

Example 3

  According to conventional techniques, a skin-softening cream of the facial muscles having the following weight composition is prepared.

  Marshmallow Root Extract (Althea officinalis) 5.0 Glycerin 5.0 Phenoxyethanol 0.5 Tetrasodium EDTA 0.05 Butylene Glycol 1.0 Carbomer 0.2 Free Tocopherol 0.7 Self-emulsifying Behenic Alcohol 5.0 Octyl Dodecanol 4 , 0 Cetyl Palmitate 2.0 Rosehip Oil Muscat 1.0 Trometamine 0.2 Matrixyl 3.0 Preservatives 0.3 Fragrance 0.2 Demineralized water qs 100.0 2871381 12

Example 4

  The study of the effects of the marshmallow extract (Althea officinalis) according to the present invention was made on ganglions of the dorsal root of rats, as indicated above.

  Experimental protocol Dorsal root ganglia cultures were established from samples taken from rat fetuses after 14 days of gestation. The ganglions that have been removed as sterile as possible are stored in an antibiotic buffer. The ganglia were cultured in DMEM medium containing fetal calf serum for 17 days. During this period of culture, the ganglia emitted dendrite extensions that secrete neuropeptides.

  After 17 days of culture, the medium was removed and fresh medium was added, either alone or added with different concentrations of the extract according to the invention. The dishes were incubated for 24 hours at 37 ° C. in an oven at 95% oxygen and 5% at 00 ° C.

  At the end of the incubation period (24 hours), the culture medium was recovered. Neuropeptides (substance P, CGRP, adrenaline and acetylcholine) were determined using a specific monoclonal antibody.

  Substance P Assay The primary cultures of nerve cells are established from samples taken at the level of the dorsal ganglion of mouse fetuses as indicated above. The cells are incubated in the presence or absence of the product under study. At the end of the incubation time, the medium is removed, and the substance P is assayed by immunological reaction with monoclonal antibodies specific for this neuropeptide.

  The test is conducted in triplicate after 24 hours of treatment.

  S lot 1: negative control S lot 2: positive control (Capsaicin induction) S lot 3: treated with Marshmallow Extract (3 concentrations) The results are summarized in the table below: Substance P (pg / ml) ) Percentage Control 42.8 7.4 - Positive Control Capsaicin 64.5 11.4 +51 (25.M) Marshmallow Extract (0.1%) 41.3 10 (ns) Marshmallow Extract (0.5%) ) 37, 49, 3 ** -12 Marshmallow Extract (1%) 31, 7 6, 8 * -26 * Significantly different from control p <0.01 (Wilcoxon Rank Sum Test).

  ** Significantly different from control p <0.05 (Wilcoxon Rank Sum Test).

  CGRP assay Primary cultures of nerve cells are obtained in the same way as for substance P and the CGRP assay is done by immunological reaction with monoclonal antibodies specific for CGRP. The assay is conducted in triplicate after 24 hours. treatment.

  lot 1: negative control lot 2: positive control (Capsaicin induction) lot 3: treated with Marshmallow Extract (3 concentrations) The results are summarized in the table below: CGRP (pg / ml) Percentage Control 290 15.8 - Positive Control Capsaicin 345 9.7 +19 (25pM) Marshmallow Extract (0.1%) 285 18.2 (ns) Marshmallow Extract (0.5%) 217 9, 3 * -25 Extract marshmallow (1%) 202 10.5 * -30 * Significantly different from control p <- 0.01 (Wilcoxon Rank Sum Test).

  Determination of Acetylcholine The nerve cells are inoculated as before. The cells are incubated in the presence or in the absence of the marshmallow extract according to the invention. At the end of the incubation time, the medium is removed and the acetylcholine is assayed by immunological reaction with specific monoclonal antibodies.

  The test is conducted in triplicate after 24 hours of treatment.

  S lot 1: negative control Lots 2-4: treated with Marshmallow Extract (3 concentrations) The determination of acetylcholine is determined using the AmplexTM Red kit (Acetylcholine / Acetylcholinesterase) which provides an ultrasensitive method. Potential uses of this kit include screening of acetylcholine esterase inhibitors and measurement of acetylcholine release from synaptosomes.

  The acetylcholine assay is evaluated using a microplate reader using excitation at 560 nm and fluorescence detection at 590 nm.

  The results are summarized in the table below: Acetylcholine (pM) Percentage Control 23.5 2.8 - Marshmallow extract (0.1%) 23.6 1.7 (ns) Marshmallow extract (0.5%) ) 19, 1 3.5 * -18 Marshmallow Extract (1%) 18, 4 1, 6 * -21 * Significantly different from p <-0.01 (Wilcoxon Rank Sum Test).

  Evaluation of the affinity towards the substance P receptor at the level of human keratinocytes in culture The keratinocytes are incubated in the presence or in the absence of the product under study or non-radioactive ligand (Sar9, Met ( 02) 1I) -SP, with 3H (Sar9, Met (O2) 11) -SP.

  After incubation, the radioactivity is assayed to determine the potential of the product under study to compete with the substance P. The assay is conducted in triplicate after 24 hours of treatment.

  lot 1: negative control lots 2-4: treated with Marshmallow Extract (3 concentrations) This study is based on the competition of Marshmallow Extract with labeled substance P. This result results in a decrease in the specific binding of the labeled substance P on its receptor when the product enters into competition.

  The results are summarized in the table below: Cpm Percentage Control 1580 124 - Marshmallow Extract (0.1%) 1298 89 * -17 Marshmallow Extract (0, 5%) 1155 113 * -26 Marshmallow Extract (1 %) 1098 104 * -30 * Significantly different from control p <- 0.01 (Wilcoxon Rank Sum Test).

  Thus, the results set out above, show that the tested product: inhibits the release of the substance P, at concentrations 0.5% and 1% respectively of 12% and 26% compared to the untreated control.

  It inhibits the release of CGRP at concentrations of 0.5% and 1% respectively by 25% and 30% relative to the untreated control.

  It inhibits the release of acetylcholine at 0.5% and 1% respectively by 18% and 21% relative to the untreated control.

  It inhibits the release of substance P on its receptor at concentrations 0.1%, 0.5% and 1% respectively of 17%, 26% and 30%.

  These results show that the test product can eliminate the activity of substance P and CGRP, inhibiting their release and competing with substance P with its receptor. This activity at the neuropeptide level and more precisely the inhibition of their release may be due to the inhibition of acetylcholine.

  In fact, it has been shown that acetylcholine can activate nociceptive C-fibers with the consequent increase in the concentration of CGRP and substance P. These results highlight the relaxing effect of muscle fibers exerted by the marshmallow extract of the invention.

Claims (1)

17 CLAIMS   1. Cosmetic and / or dermatological composition for topical application, intended to combat the signs of cutaneous aging, characterized in that it comprises an effective amount of a marshmallow extract (Althea officinalis).   2. Composition according to claim 1, characterized in that the extract is obtained from marshmallow roots (Althea officinales).   3. Composition according to claim 2, characterized in that the extract is in aqueous form.   4. Composition according to claim 3, characterized in that the extract is obtained by leaching from marshmallow roots (Althea officinalis) reduced to powder.   5. Composition according to any one of the preceding claims, characterized in that the marshmallow extract (Althea officinalis) is a liquid characterized by: - dry matter 1.5 to 2% - water - density refractive index - pH - neutral oses - acidic oses 98 to 98.5% 0.993 to 1.00 6.0 to 6.2 839 mg / L 459.8 mg / L 6. Composition according to any one of the preceding claims-25, characterized in that it comprises between 0.2 and 10% by weight of marshmallow extract.   7. Composition according to any one of the preceding claims, characterized in that it further comprises endorphin-producing substances, extracts of Bacopa monieri, Boswelia serrata, mint piperata, amaranth seed proteins ( Amarantus caudatus) or pea globulins, Calophylum oil, an oil rich in A7 sterols, an unsaturated oil rich in omega 3 and 2871381 18 6, or maize proteins, Imperata cylindrica, Echium oil, a palmitoyl pentapeptide-3 or derivatives such as palmitoyl GHK and palmitoyl GQPR or palmitoyl VGVAPG combined with a ceramide-2, as well as a ceramide.   8. Use of a marshmallow extract (Althea officinalis) for the preparation of a topical composition for combating the signs of skin aging.   9. Cosmetic process for combating the signs of aging of the skin, comprising applying to the areas of the skin affected a composition containing an effective amount of the topical composition according to any one of claims 1 to 7.   10. Use of a marshmallow extract (Althea officinalis) for the preparation of a dermatological drug for the prevention and treatment of uncontrolled facial muscular contractions.