FR2871380A1 - Topical cosmetic and/or dermatological composition, used to fight against signs of cutaneous ageing and to prevent/treat uncontrolled facial muscular contractions, comprises blue lotus extract - Google Patents

Abstract

Topical cosmetic and/or dermatological composition (A) to fight against signs of cutaneous ageing, comprises a blue lotus extract (I) (Nymphaea caerulea). Independent claims are also included for: (1) use of (I) in the preparation of (A) to fight against signs of cutaneous ageing; (2) cosmetic process comprising application of (A) on the zones of the affected of the skin; and (3) use of (I) for the preparation of a dermatological medicament for the prevention or treatment of uncontrolled facial muscular contractions. ACTIVITY : Relaxant; Dermatological. MECHANISM OF ACTION : Neurotransmitter inhibitor; P substance inhibitor. The ability of (A) to inhibit substance P was tested in rats using biological assays. The results showed that the (A) significantly inhibited the release of substance P.

Description

The present invention relates to a new cosmetic composition and / or

  dermatological agent for preventing and treating the signs of skin aging, and more particularly a blue lotus composition with a relaxing effect of

  the skin, able to act effectively against the facial muscular contractions responsible for the signs of cutaneous aging and in particular the wrinkles of expression.

  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.

  B1499en 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, expression wrinkles are caused by multiple contractions and twitches that occur daily facial features under the action of the subcutaneous muscles of the face that contract and releasing successively incessantly following the rhythm of 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 to be able to have new alternative topical compositions which make it possible to effectively combat the effects of cutaneous aging, and in particular topical compositions based on appropriate plant extracts derived more particularly from plants known for their favorable properties. .

  In accordance with the present invention, it has been found that it is possible to act effectively against facial muscle contractions responsible for the signs of skin aging, and in particular expression lines, by using topical extracts-based compositions. of blue lotus (Nymphaea caerulea).

  The subject of the present invention is therefore a novel cosmetic and / or dermatological composition based on plants, and more particularly based on blue lotus extract (Nymphaea caerulea) having effects of inhibition of uncontrolled facial muscular contractions. origin of expression lines.

  The subject of the present invention is also the use of a blue lotus extract (Nymphaea caerulea) for the preparation of a topical composition intended to combat the signs of cutaneous aging, and in particular the expression lines caused by uncontrolled facial muscular contractions.

  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 composition containing an effective amount of the topical composition according to the present invention.

  The invention also relates to the use of a blue lotus extract (Nymphaea caerulea) for the preparation 3o 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 blue lotus extract (Nymphaea caerulea) in an amount effective for combating the signs of skin aging, and more particularly expression wrinkles, as well as acceptable carriers and excipients in dermatology and cosmetology.

  The blue lotus (Nymphaea caerulea) was already used in ancient Egypt for its sweet scent, and its root was consumed as a food product. Nymphaea, especially the lotus, and water lilies contain, in all parts, water lily and nupharine (which are alkaloids) as well as other ill-defined components.

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

  The blue lotus plant 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 acetylcholine. 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: E a decrease up to 41% of the substance P, É a decrease up to 36% of the CGRP (Calcitonin Gene Related Protein), É a decrease of up to 37% of acetylcholine, a decrease of up to 30% in the affinity of the substance P receptor in human keratinocytes in culture, a -24% inhibition of the reception of the epinephrine on the adrenergic receptor.

  These results were obtained with a blue lotus extract (Nymphaea caerulea), and confirm that, in topical application, a blue lotus extract, or a composition containing it, exhibits a muscle relaxation effect.

  The tests carried out by the Applicant have shown that, among the various parts of the plant, it is preferable to use the mature seeds, whose supply and preservation do not generally raise any technical difficulty.

  According to an advantageous embodiment, the extract that can be used in the invention is obtained by hydroalcoholic or hydroglycolic maceration of pulverized seeds, and preferably in a propylene glycol / water mixture in a ratio (v / v) of about 50. / 50.

  The extract is in the form of a brown-black liquid and is characterized by: The tests were performed using 0.1%, 0.5% and 1% extract, respectively.

  The results are explained in Example 4 below.

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

  According to an advantageous embodiment, the blue lotus 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-inflammatory effects. age of the composition. Thus, it is particularly advantageous to combine it with appropriate amounts of amaranth seed protein (Amarantus caudatus) or pea globulins in order to obtain a skin tightening effect, dry matter oil 2 to 2, 5% - density 1.019 - refractive index 1.393 - pH 6, 2 to 6, 6 Calophylum to enhance the anti-wrinkle effect of Imperata cylindrica, eg MOIST 24 from Sederma, to promote hydration skin by modification of the osmotic pressure, Echium oil for its anti-inflammatory effect, or palmitoyl pentapeptide-3 such as Matrixyl or derivatives such as palmitoyl GHK (possessing the glycyl-Histidyl chain Lysine) and palmitoyl GQPR (Glycyl-Glutamyl-Prolyl-Arginine) or palmitoyl VGVAPG (Valyl-Glycyl-Valyl-Alanyl-Prolyl-Glycine) combined with a ceramide-2, and generally any association with a ceramide.

  The compositions according to the present invention may be in any of the usual galenical forms suitable for topical application.

  They may comprise between 0.2% and 10% by weight of blue lotus 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, preferably of the order of 0.5 to 1%, are preferably used while spot treatment may require higher doses.

  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 gel, lotion, emulsion (in particular cream or milk), mask or ointment, containing excipients. and common compatible and pharmaceutically acceptable carriers. They may also be in the form of wipes soaked with a solution containing the lotus 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 excipients suitable 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 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 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.

  Blue lotus seed extract 3.0 Glycerin 5.0 2-methyl 1,3-propane diol 5.0 Phenonip 0.5 Panthenol 0.2 Allantoin 0.1 PEG 40 castor oil 1.5 Dipropylene glycol 1.0 Perfume 0.5 Demineralized water qs 100.0 The blue lotus seed extract used in the above composition is a hydro-glycolic extract obtained by maceration of seeds sprayed in a propylene glycol / water 50/50 mixture (v / v). v) having the characteristics indicated above.

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

Example 2

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

  Blue Lotus Seed Extract 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 2871380 Octyl Dodecanol 4, 0 Cetyl palmitate 2.0 Rosehip oil Muscat 1.0 Trometamine 0.2 Matrixyl 3.0 Preservatives 0.3 Perfume 0.2 Demineralised water qs 100.0 The blue lotus seed extract used in the composition below above is identical to that of Example 1.

Example 3

  A facial tissue lightening wipe is prepared with a lotion having the following weight composition. Blue Lotus Seed Extract 5.0 Glycerin 5.0 PEG 400 4.0 Sorbitol 7o% 2.0 Butylene Glycol 4.0 Phenonip 0.5 Water-soluble Fragrance 1.0 Demineralized Water qs 100.0

Example 4

  The study of the effects of the blue lotus extract according to the present invention was made on dorsal root ganglia 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 sterilely 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% CO2.

  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 S lot 3: treated with 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 (25pM) Blue lotus extract (0, 1%) 36.8 12 ** -14 Blue lotus extract (0.5%) 31.8 7.8 * -25 ( Capsaicin induction) Product Blue Lotus Extract (3 Blue lotus extract (1%) 25.2 8.2 * -41 * Significantly different from control p <-0.05 (Wilcoxon Rank Sum Test).

  ** Significantly different from control p <0.01 (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.

  S lot 1: negative control S lot 2: positive control (Capsaicin induction) S lot 3: treated with the product Blue Lotus 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 (25e) Blue lotus extract (0.1%) 215 15.8 * -25 Blue lotus extract (0.5%) 202 22 * -30 Blue lotus extract {1%) 185 34 * -36 * Significantly different from p0.01 (Wilcoxon Rank Sum Test).

  Determination of acetylcholine The nerve cells are seeded as before. The cells are incubated in the presence or in the absence of the blue lotus 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 S lot 2-4: treated with the product Lotus extract (3 concentrations) The determination of acetylcholine is determined using the AmplexTM Red kit (Acetylcholine / Acetylcholinesterase) which provides a method very sensitive. 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 - Blue lotus extract (0.1%) 20, 8 0, 7 -11 (ns) Blue lotus extract ( 0.5%) 16.7 2.5 * -29 Blue lotus extract (1%) 14.8 3, 2 * -37 * Significantly different from control 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 ( O2) 1l) -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 test is conducted in triplicate after 24 hours of treatment.

  S lot 1: negative control S lot 2-4: treated with Blue Lotus Extract (3 concentrations) This study is based on the competition of Blue Lotus 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 - Blue lotus extract (0.1%) 1205 32 * -23 Blue lotus extract (0.5%) 1212 102 * -23 Lotus extract blue (1%) 1113 135 * -30 * Significantly different from Io p <0.01 (Wilcoxon Rank Sum Test).

  Thus, the results set out above show that the product tested: inhibits the release of substance P at concentrations of 0.5% and 1% respectively by 25% and 41% relative to the untreated control.

  It inhibits the release of CGRP at concentrations of 0.5% and 1% respectively by 30% and 36% relative to the untreated control.

  inhibits the release of substance P on its receptor at concentrations 0.1%; 0.5% and 1% respectively of 23% and 30%.

  It inhibits the release of acetylcholine at concentrations of 0.5% and 1% respectively by 29% and 37% relative to the untreated control.

  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 specifically the inhibition of their release may be due to the inhibition of acetylcholine.

  Indeed it has been shown that acetylcholine can activate the nociceptive C fibers with, consequently, an increase in the concentration of CGRP and substance P. Adrenaline assay The results obtained after treatment of the same cells as in the The above blue lotus extract assays of the invention show competition of the extract with adrenaline from the adrenergic receptor. This attachment to the adrenergic receptor may regulate the mechanism of contractility via calmodulin. The affinity of the calmodulin calcium complex for the ATPase of myosin depends on the degree of phosphorylation of a myosin light chain kinase. When this is phosphorylated by the action of protein kinase A, the affinity of the calcium-calmodulin complex for myosin ATPase decreases, resulting in relaxation of the muscle fibers.

  The results are summarized in the table below: [125I] -Adrenaline percentage (Cpm) Control 3850 270 - Blue lotus extract (0.1%) 3415 211 -11 Blue lotus extract (0.5%) 3218 198 * -16 Blue lotus extract (1%) 2915 153 * -24 * Significantly different from the control p <- 0.05 (Wilcoxon Rank Sum Test).

  These results highlight the relaxing effect of muscle fibers exerted by the blue lotus extract of the invention.

Claims (10)

  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 blue lotus extract (Nymphaea caerulea).   2. Composition according to claim 1, characterized in that the extract is obtained from blue lotus seeds (Nymphea caerulea).   3. Composition according to claim 2, characterized in that the extract is obtained by hydro-glycolic maceration of pulverized seeds.   4. Composition according to claim 3, characterized in that the extract is obtained by maceration of seeds sprayed in a propylene glycol / water mixture.   5. Composition according to any one of the preceding claims, characterized in that the blue lotus extract (Nymphaea caerulea) is a brown-black liquid characterized by: - dry matter 2 to 2.5% density 1.019 - index of refraction 1.393 - pH 6, 2 to 6, 6 6. Composition according to any one of the preceding claims, characterized in that it comprises between 0.2 and 10% by weight of blue lotus extract.   7. Composition according to any one of the preceding claims, characterized in that it further comprises amaranth seed proteins (Amarantus caudatus) or pea globulins, Calophylum oil, Imperata cylindrica. , Echium oil, palmitoyl pentapeptide-3 or derivatives such as palmitoyl GHK and palmitoyl GQPR or palmitoyl VGVAPG combined with a ceramide-2, and a ceramide.   8. Use of a blue lotus extract (Nymphaea caerulea) 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 blue lotus extract (Nymphaea caerulea) for the preparation of a dermatological drug for the prevention and treatment of uncontrolled facial muscular contractions.