FR2871382A1 - Topical cosmetic/dermatological composition, useful to fight against the signs of aging, comprises a complex extract of blue lotus and poppy - Google Patents

Abstract

Topical cosmetic and/or dermatological composition (I), to fight against aging of the skin, comprising a complex extract of blue lotus (A) ( Nymphaea caerulea) and poppy (B) ( Papaver rhoeas), is new. ACTIVITY : Relaxant; Dermatological. MECHANISM OF ACTION : Facial muscular contraction inhibitor; Neurotransmitter inhibitor. The ability of (I) to inhibit neurotransmitters activity was tested in ganglion of foetus of mouse. The results showed that (I) reduced the phosphorus (16 %), calcitonine gene related protein (CGRP) (23 %), acetyl choline (16 %) and jusqula (5 %).

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 composition based on a complex of plant extracts with

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

  The skin constitutes 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 to adapt to the conditions of its 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.

  B1500en 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.

  Some 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 wrinkles, by using topical compositions based on complex d extracts of blue lotus (Nymphaea caerulea) and poppy (Papaver rhoeas).

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

  The present invention also relates to the use of a complex of blue lotus extract (Nymphaea caerulea) and poppy extract (Papaver rhoeas) for the preparation of a topical composition for combating the signs of aging skin, and in particular 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 complex of blue lotus extract (Nymphaea caerulea) and poppy extract (Papaver rhoeas) for the preparation of a dermatological drug for the prevention and treatment of contractions uncontrolled facial muscles.

  The compositions according to the present invention are distinguished in that they comprise a complex of blue lotus extract (Nymphaea caerulea) and poppy extract (Papaver rhoeas) 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.

  The poppy (Papaver rhoeas) contains rhoeadine, an alkaloid of the tetrahydrobenzazepine series, which is believed to have neuroleptic properties. This plant has been described as being used in cases of cardiac erritism in adults, as a calming agent in adults and children, and also for the symptomatic treatment of cough.

  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. .

  Complexes of plant extracts of blue lotus and poppy used in the compositions according to the present invention have shown in vitro tests of neurotransmitter inhibition effects capable of generating reflex muscle contractions, thanks to neuropeptides whose modulation is related to the production of acetyl choline and adrenaline. The tests were performed on a dorsal ganglion culture of mouse fetus.

  The results, detailed below, showed, according to the concentrations used: E a decrease up to 16% of substance P, É a decrease up to 23% of the CGRP (Calcitonin Gene Related Protein), É a decrease of up to 16% in acetyl choline; a decrease of up to 35% in the affinity of the substance P receptor for human keratinocytes in culture; furthermore, an effect of inhibition of adrenaline reception on the adrenergic receptor.

  These results were obtained with a complex of blue lotus extract (Nymphaea caerulea) and poppy extract (Papaver rhoeas), and confirm that, in topical application, a blue poppy / lotus complex according to the invention, or a composition containing it, has a muscular relaxation effect.

  The tests carried out by the applicant have shown that among the various parts of the plant, both for the poppy and for the blue lotus, it is preferable to use the mature seeds, the supply and preservation of which do not generally raise technical difficulty.

  According to an advantageous embodiment, the poppy and blue lotus extracts that can be used in the invention are obtained by hydroalcoholic or hydroglycolic maceration of pulverized seeds, and preferably in a propylene glycol / water mixture in a ratio (v / v ) close to 50/50 for each of the two extracts.

  The blue lotus extract is in the form of a black brown liquid, and is characterized by: - dry matter 2 to 2.5% - density 1.019 refractive index 1.393 - pH 6.2 to 6.6 L poppy extract is in the form of a pale yellow liquid, and is characterized by: dry matter 0.05 to 0.6% - density 1.010 to 1.060 - refractive index 1.375 to 1.395 - pH 6.5 to 7, The tests were carried out using 0.1%, 0.5% and 1% complex samples at 50% by weight of blue lotus and 50% by weight of poppy.

  The results are explained in Example 4 below.

  The weight ratio of the poppy extract to the blue lotus extract may vary from about 1/4 to 4/1 and is preferably about 1: 1. The two extracts in liquid form are mixed to form the complex.

  The poppy / blue lotus complex 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 mask 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 inhibition of facial muscle contractions or to supplement the anti-aging effects of the composition. Thus, it is particularly advantageous to combine it with appropriate quantities of amaranth seed protein (Amarantus caudatus) or pea globulins to obtain a skin tightening effect of Calophylum oil to enhance the effect. anti-wrinkles, of Imperata cylindrica, for example MOIST 24 from Sederma, in order to promote the hydration of the skin by modification of the osmotic pressure, of the 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 combination with a ceramide.

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

  They may comprise between 0.2% and 10% by weight of complex 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 of about 0.5 to 1% are preferably used, while occasional 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, 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 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 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 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, palmitate cetyl, cetyl phosphate; emulsifiers; preservatives such as phenoxyethanol, methyl parahydroxybenzoate (methylparaben), ethyl parahydroxybenzoate (ethylparaben), propyl paraben (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 / poppy complex 3.0 Glycerin 5.0 2-methyl 1,3-propane diol 5.0 Phenonip Panthenol Allantoin PEG 40 Castor oil Dipropylene glycol Fragrance Demineralized water The complex used in the above composition comprises an extract of hydro-glycolic blue lotus seeds Io and a hydro-glycolic poppy extract, both obtained by maceration of seeds sprayed in a 50/50 (v / v) propylene glycol / water mixture.

  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 cream is obtained which relaxes the facial muscles having the following weight composition.

  Blue Lotus / Poppy Complex 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 Palmitate cetyl 2.0 Rosehip oil Muscat 1.0 Tromethamine 0.2 Matrixyl 3.0 Preservatives 0.3 Perfume 0.2 Demineralized water qs 100.0 The blue / poppy lotus complex used in the above composition is identical to the of Example 1.

Example 3

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

  Blue Lotus / Poppy Complex 5.0 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 4

  The study of the effects of the blue lotus and poppy complex 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 from the mouse fetal dorsal ganglion 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) 20 S lot 3: treated with the product Lotus Blue 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) Poppy / lotus complex 43.7 9.8 (ns) (0.1%) Poppy / lotus complex 38.5 10.1 (ns) (0, 5%) Poppy / lotus complex 35.8 7.4 * -16 (1%) * 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.

  S lot 1: negative control E lot 2: positive control (Capsaicin induction) 10 ^ 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 (25 M) Poppy / lotus complex 296 21.5 (ns) (0, 1%) Poppy / lotus complex 245 11.8 ** - (0, 5%) Poppy / lotus complex 223 25.8 * -23 (1%) * Significantly different from control p <-0.01 (Wilcoxon Rank Sum Test).

  ** Significantly different from control p <- 0.05 (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 25 treatments.

  S lot 1: negative control 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 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 (gM) Percentage Control 23.5 2.8 - Poppy / lotus complex 22.8 3.5 (ns) (0, 1%) Poppy / lotus complex 20.5 1.5 * -12 (0.5%) Poppy / lotus complex 19.6 2.2 * -16 (1%) * Significantly different from control p <0.05 (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) 11) -SP, with the 3H (Sar9, Met (02) 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 the poppy / blue lotus complex (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 - Poppy / lotus complex 1113 + 122 * -29 {0, 1%) Poppy / lotus complex 1123 185 * -29 (0, 5%) Poppy complex / lotus 1025 + 202 * -35 (1%) * Significantly different from the control (Wilcoxon Rank Sum Test).

  Thus, the results set out above, show that the so produced product tested: inhibits the release of the substance P, at the concentrations 0.5% and 1% respectively of 10% and 16% compared to the untreated control.

  inhibits the release of CGRP at 0.5% and 1% respectively by 15% and 23% relative to the untreated control.

  inhibits the release of acetylcholine, at 0.5% and 1% respectively by 12% and 16% relative to the untreated control.

  inhibits the release of substance P on its receptor at 0.1% concentrations; 0.5% and 1% respectively of 29%, 29% and 35%.

  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.

  Indeed, it has been shown that acetylcholine can activate nociceptive C-fibers with, consequently, an increase in the concentration of CGRP and substance P. These results highlight the relaxing effect of muscle fibers exerted by the poppy / blue lotus complex of the invention.

Claims (11)

  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 complex of blue lotus extract (Nymphaea caerulea) and poppy (Papaver rhoeas).   2. Composition according to claim 1, characterized in that the extract is obtained from seeds of blue lotus (Nymphea caerulea) and poppy seeds (Papaver rhoeas).   io 3. Composition according to claim 2, characterized in that the extracts are obtained by maceration glycolic sprayed seeds.   4. Composition according to claim 3, characterized in that the extracts are obtained by maceration of seeds 15 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) used in the complex is a brown-black liquid characterized by: dry matter 2 to 2.5% - density 1,019 - refractive index 1,393 - pH 6.2 to 6.6 6. Composition according to any one of the preceding claims, characterized in that the poppy extract (Papaver rhoeas) used in the complex is a pale yellow liquid characterized by: - dry matter 0.05 to 0.6 % - density 1,010 to 1,060 refractive index 1,375 to 1,395 - pH 6.5 to 7.5 7. Composition according to any one of the preceding claims, characterized in that it comprises between 0.2 and 10% by weight of complex.   8. 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, lamb 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.   9. Use of a complex of blue lotus extract (Nymphaea caerulea) and poppy extract (Papaver rhoeas) for the preparation of a topical composition for combating the signs of skin aging.   10. A cosmetic method 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 one of the   any of claims 1 to 8.   11. Use of a complex of blue lotus extract (Nymphaea caerulea) and poppy extract (Papaver rhoeas) for the preparation of a dermatological drug for the prevention and treatment of uncontrolled facial muscular contractions.