EP1641433A1 - Novel dermatological and/or cosmetologic hydrating and anti-irritation compositions - Google Patents

Novel dermatological and/or cosmetologic hydrating and anti-irritation compositions

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Publication number
EP1641433A1
EP1641433A1 EP03767863A EP03767863A EP1641433A1 EP 1641433 A1 EP1641433 A1 EP 1641433A1 EP 03767863 A EP03767863 A EP 03767863A EP 03767863 A EP03767863 A EP 03767863A EP 1641433 A1 EP1641433 A1 EP 1641433A1
Authority
EP
European Patent Office
Prior art keywords
cosmetic compositions
compositions according
dermatological
skin
new
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP03767863A
Other languages
German (de)
French (fr)
Inventor
Luc Lefeuvre
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Laboratoire Biorga
Original Assignee
Laboratoire Biorga
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Filing date
Publication date
Application filed by Laboratoire Biorga filed Critical Laboratoire Biorga
Publication of EP1641433A1 publication Critical patent/EP1641433A1/en
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/74—Synthetic polymeric materials
    • A61K31/785—Polymers containing nitrogen
    • A61K31/787—Polymers containing nitrogen containing heterocyclic rings having nitrogen as a ring hetero atom
    • A61K31/79—Polymers of vinyl pyrrolidone
    • 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
    • A61K8/55—Phosphorus compounds
    • A61K8/553—Phospholipids, e.g. lecithin
    • 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
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
    • A61K8/817—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen; Compositions or derivatives of such polymers, e.g. vinylimidazol, vinylcaprolactame, allylamines (Polyquaternium 6)
    • A61K8/8176—Homopolymers of N-vinyl-pyrrolidones. Compositions of derivatives of such polymers
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/70—Biological properties of the composition as a whole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/74—Biological properties of particular ingredients
    • A61K2800/75—Anti-irritant
    • 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
    • A61Q19/007—Preparations for dry skin

Definitions

  • the present invention relates to the field of chemistry and more particularly to the field of dermatology and cosmetics.
  • compositions with protective surface or repairing action, based on two active principles which contribute to preserving or recovering epidermal homeostasis.
  • compositions intended to exert a barrier effect against irritating or allergenic exogenous agents and to play a skin protection role, characterized in that they contain as active principles a homopolymer of N- vinyl 2-pyrrolidone " and a copolymer ⁇ de'2-methacryloxy ethyl phosphoryl choline-n-butyl methacrylate associated with or in admixture with one or more excipients or inert, non-toxic dermatologically acceptable vehicles.
  • the copolymer of 2-methacryloyloxy ethylphosphoryl choline / butyl methacrylate has a structure similar to that of the polar group of phospholipids on the cell membrane and as such it is perfectly biocompatible.
  • PMPC This copolymer called PMPC is characterized by the presence in its polymerized structure of branches of polar phospholipids and can be integrated in depth, up to a distance of 10 ⁇ m, into the lamellar structures, organized in a similar manner, of the skin barrier so stabilize, repair, or restore them. Its action is completely “bio-mimetic”. Its composition makes it a perfectly “biocompatible" active ingredient.
  • the PMPC Once integrated into the skin barrier, the PMPC also has the capacity to retain water and maintain an ideal rate of hydration to ensure good plasticity of the stratum corneum. Its water retention power, compared to that of hyaluronic acid or that of sodium pyrrolidone carboxylate, is superior to these two reference hydrating active ingredients.
  • PIE Insensitive Water Perspiration
  • PMPC on the surface of the epidermis, also has a pronounced "anti-adhesion" effect with respect to proteins. As these are often allergenic molecules, PMPC could therefore protect against contact allergies, of protein origin.
  • the PMPC has shown its protective skin effect against irritations triggered by Alpha Hydroxy-carboxylic Acids (A.H.A.) such as glycolic acid or lactic acid.
  • Alpha Hydroxy-carboxylic Acids such as glycolic acid or lactic acid.
  • PNP polyvinyl pyrrolidone
  • Polyvinylpyrrolidone is defined chemically as being a homopolymer of ⁇ - Ninyl 2-pyrrolidone, the formula of which is:
  • PNP has, for example, been used for a long time in combination with iodine in order to make the use of iodine less dangerous, while retaining its antiseptic activity. PNP also considerably prolongs the effectiveness of certain drug active ingredients. It brings a persistence of activity. We have also described its protective power of the mucous membranes against bacterial toxins.
  • PVP makes it possible to greatly reduce the irritations and sensitizations induced by phenols, to reduce the irritations triggered by detergents and by A.H.A. and reduce the toxicity induced by Formaldehyde.
  • the system according to the invention consists on the one hand, of a polymer of Ninyl-Pyrrolidone (PNP) and on the other hand, of a polymer of Phosphoryl Choline (PMPC) in a suitable excipient.
  • PNP Ninyl-Pyrrolidone
  • PMPC Phosphoryl Choline
  • the system associating PMPC and PNP is not only a surface protective agent, isolating the skin from irritant or sensitizing exogenous agents. (protein allergens, bacterial toxins, detergents, acids, solvents, etc.) but also a system which promotes repair by "biomimicry" of the skin barrier and which provides it with optimal hydration which allows it to regain its balance.
  • the skin distributed over the entire body surface, is first of all a protective organ of the underlying tissues, against external aggressions. This protection is provided by a particularly effective physical barrier, the stratum corneum, the most superficial layer of the epidermis. It consists of a hydro-lipidic surface film and several layers of very keratinized dead cells, the Cornéocytes. These cells are welded together by inter-corneocytic cement. This set constitutes a real "anti-aggression" wall and it is essential to maintain its integrity.
  • the living epidermis ensures on the one hand the cell multiplication and differentiation which makes it possible to constitute a good quality corneal barrier and on the other hand functions of active protection when external stresses manage to pass through the stratum corneum.
  • UV radiation will stimulate Melanogenesis, the purpose of which is to absorb, thanks to melanin, as much UN rays as possible to avoid damage to living, epidermal and dermal tissues.
  • the epidermis can also release "defensins" under the influence of aggressions, always to protect itself.
  • the active double protection system is an original association of two substances, one acting on the surface, the second acting in the depth of the stratum corneum.
  • the system which is the subject of the present invention contributes to ensuring the preservation of epidermal homeostasis, at least to a return to this fragile state of equilibrium.
  • the excipient is a diluent, mineral or organic agent, a mineral or organic filler, a binding agent, a flow agent or an agent giving the pearly luster.
  • a vehicle is a liquid, pasty or viscous mixture which allows the transport of the preparation in contact with the skin, the integuments or the mucous membranes.
  • the vehicle may be water or an aqueous liquid, an oily product, a silicone and / or an organic solvent.
  • liquid or fluid compositions which are the subject of the present invention, mention may be made of creams, ointments, anhydrous or aqueous gels, lotions, O / W or W / O emulsions, breads, soaps, milks for shower and the like.
  • compositions according to the invention contain 0.1 to 4% of polyvinyl pyrrolidone with preferably 1.5 to 2.5%.
  • PMPC is present in the compositions in an amount ranging from 0.1 to 4% relative to the total composition, with a preference of the order of 1.8 to 2.5%.
  • compositions according to the invention may also contain silicones which improve the stability of the emulsions and ensure a feeling of softness for the skin during application, thickening agents, diluents, penetration agents, flavoring agents and / or preservatives.
  • thickening agents mention may be made of natural or synthetic gums, cellulose derivatives, swelling clays of the Bentone type, acrylic acid polymers, acrylic amide polymers, N-alkyl (polyhydroxyl akyl) glucuronamides, starches, modified starches, polysaccharides, dextrins, lamellar silicates and the like.
  • mineral salts which are insoluble or poorly soluble in water, such as alkaline earth metal carbonates, magnesium or zinc, alkali metal or alkaline earth metal titanates, titanium dioxide , metal oxides such as iron oxides, zinc oxide, tin oxide, alkaline earth metal sulfates such as calcium sulfate or barium sulfate, mono-, di- or tri-basic like calcium hydrogen phosphate, tricalcium phosphate or magnesium phosphate.
  • alkaline earth metal carbonates magnesium or zinc
  • alkali metal or alkaline earth metal titanates titanium dioxide
  • metal oxides such as iron oxides, zinc oxide, tin oxide
  • alkaline earth metal sulfates such as calcium sulfate or barium sulfate, mono-, di- or tri-basic like calcium hydrogen phosphate, tricalcium phosphate or magnesium phosphate.
  • aliphatic lactams such as caprolactam
  • fatty acids such as oleic acid
  • fatty alcohols such as lauric alcohol or pelargomic alcohol
  • dioxolane derivatives such as dimethyl dioxolane or methylnonyldioxolane.
  • the flavoring agent may be an essence or an essential oil or a perfume concentrate, obtained from the leaves, flowers, buds, roots or barks of odorous plants. It is also possible to use one or more of the constituents of these essences obtained by distillation, separation, by chromatography or even by synthesis.
  • Advantageous flavoring products are, for example, benzoic aldehyde, cinnamic aldehyde, eugenol, cineol or lavandinol.
  • liquid compositions will be added with one or more preserving agents among which the esters of p-hydroxybenzoic acid, the esters of salicylic acid, sorbic acid, derivatives of urea, phenols, coumaric acid or benzyl alcohol.
  • compositions according to the invention are prepared according to methods customary in cosmetology by mixing, by grinding or by fusion of the active principles and incorporation into an excipient or a vehicle then aromatization and distribution in packaging or bottles. of appropriate shape or volume.
  • compositions according to the invention find use as a skin protector by maintaining the integrity of the skin and by exerting a barrier effect, use as restructuring of the skin and mucous membranes after destruction, in particular by occupational injury, as an anti-allergy agent against irritation, maceration and also against hyper stimulation, in the treatment of dermatitis and in particular orthoergic dermatitis.
  • the compositions according to the invention find a more particular use for the prevention and the treatment of skin allergies due to nickel, in particular to jewelry containing nickel.
  • compositions are intended to be applied to the skin, the mucous membranes or the integuments from 1 to 4 times a day, in particular in the form of powders, milk, cream or emulsion.
  • Non-ionic surfactant sold under the brand name Arlacel PI 35 1%
  • Carbomer (Carbopol 941 from Goodrich) 0.5%
  • the purpose of this study is to determine the anti-irritant potential of the composition according to the invention on explants of human skin maintained in survival, with respect to external aggressions caused by the application of different chemicals; irritants or caustics, such as sodium lauryl sulphate, hydrochloric acid, Fair-moniac and toluene. 1 - Preparation of explants
  • composition according to the invention is applied at a rate of 2 mg / cm 2 ( 2 ⁇ l) per explant, distributed using a sterile finger pad. The application is repeated 10 min after complete drying of the product. The product is applied in two successive layers and represents a total amount of 4 mg / cm.
  • the explants are placed in HBSS (new 6-well plates).
  • Aggression by irritants is carried out by topical application of a 6 mm diameter filter paper disc on which 15 ⁇ l of product have been previously deposited.
  • PGE 2 is assayed in the culture media taken after two hours of contact with the attacking agents, by an immunoenzymatic method (EIA R&D assay kit).
  • the LDH is assayed in the culture media taken on D4, by an immunoenzymatic method.
  • I- Control skin Normal epidermal structure with a laminated and weakly keratinized stratum corneum.
  • composition according to the invention normal epidermal structure with a slightly laminated stratum corneum and weakly keratinized at the basal level.
  • III- Skin treated with the 20% SDS solution Normal epidermal structure, with a fairly compact stratum corneum, very keratinized on the surface and slightly keratinized on the basal.
  • IV- Skin treated with the composition according to the invention + SDS at 20% Normal epidermal structure with a slightly more compact stratum corneum, very keratinized on the surface and slightly keratinized on the basal.
  • composition according to the invention reduces the activity of the SDS action by showing a less compact and less keratinized stratum corneum.
  • Applying the product at the same time as a 10% HCl solution> improves the appearance of the stratum corneum (laminated and less keratinized). This improvement is identical in the presence of ammonia.
  • composition according to the invention leads to a significant reduction in the level of PEG 2 induced by the application of SDS to 20%
  • a preventive application of the composition according to the invention does not lead to a significant reduction in the level of PEG 2 induced by the application of a solution of
  • a preventive application of the composition according to the invention results in a significant reduction in the level of PEG induced by the application of a 10% ammonia solution
  • - A preventive application of the composition according to the invention results in a significant reduction the level of PEG 2 induced by the application of pure toluene.
  • the application of the product according to the invention does not induce a significant reduction in the LDH level with the 10% HCl solution, the 20% SDS and a NH 4 OH solution.
  • its application with pure toluene induces a significant reduction of the order of about 20%.
  • composition according to the invention makes it possible to note that the product induces significant protection with respect to NH4OH at 10%>, from SDS to 20%> and pure toluene.
  • compositions according to the invention induce protection against aggressions brought by SDS at 20%, by NH4OH at 10% and by HCl at 10%.
  • Contact hypersensitivity is a major health problem in most industrialized countries.
  • the most encountered allergens are the constituents of perfumes and cosmetics, topical drugs, cleaning products, dental products, laboratory products and many others.
  • Haptens are low molecular weight chemical molecules capable of interacting with amino acids present on extracellular, membrane or intracellular proteins.
  • hapten enters the epidermis it is attached by high affinity bonds to carrier molecules, then it is taken up by Langerhans cells (latency).
  • This latency phase leads to the synthesis of membrane receptors: MHC class I and class II molecules (Major Histocompatibility Complex).
  • This step is accompanied by the activation of Langerhans cells (CL) with production of cytokines. Then, the CL migrate to the nodes causing the clonal expansion of T lymphocytes (LT) which are then distributed in the various tissues of the body.
  • LT T lymphocytes
  • haptenized CL migrate in the dermis where they will present the hapten in association with the molecules of the MHC I and II, to the LT memories present in the dermis. There is then lymphocyte activation, production of Th1 cytokines, which leads to the activation of other cell types including endothelial cells and keratinocytes. This causes an allergy-like reaction.
  • LCs Langerhans cells
  • LCs provide immune surveillance for the skin and contain specific intracytoplasmic structures called Birbeck granules. Finally, they present, among other things, the very abundant CD anti-gene on their membrane.
  • the LCs migrate to the lymph nodes via the lymphatic vessels. During their movement, these cells undergo phenotypic changes: in fact, they are CD positive in the dermis and epidermis, but as they migrate they become CD negative and then express other antigens (such as HLA-DR and CD36). They also undergo morphological modifications (cells of dendritic morphology in the epidermis, more rounded in the dermis, veiled in the lymphatic channels) and functional modifications (loss of the function of dressing, acquisition of the function of presentation and lymphocyte activation). In the ganglia, they present the antigens to naive T lymphocytes and thus induce a specific primary immune response. There is therefore a circulation of CL according to the immunological conditions.
  • UVB Ultraviolet rays irradiation
  • cytokines ILl ⁇ , TNF ⁇ , GM-CSF ....
  • the molecules involved in cell signaling protein kinases C.
  • interleukins like IL4 and IL 10 inhibit the migration of CL.
  • E-cadherin a molecule belonging to the family of adhesion molecules connects LCs to keratinocytes.
  • the signals given on the one hand by cytokines and on the other hand by a hapten have been shown to decrease the expression of E-cadherin.
  • LCs "detach" from keratinocytes and can migrate to the lymph nodes).
  • Ex-vivo model explants The principle is based on the use of human skin biopsies, obtained from plastic surgery. The test substances are applied directly to the skin which is maintained at 37 ° C. Skin sections (thickness of 5 ⁇ m) are then made in order to observe, after labeling with specific antibodies (anti-CDla, anti-HLA-DR), the Langerhans cells. A significant decrease in the number of residual LCs in the epidermis is observed after the application of strong haptens while these changes are not observed after application of irritant substances.
  • the study is conducted to determine the activity of the formulation with respect to contact awareness.
  • the explants are pretreated for 48 hours with the formulation, then reference allergens are applied in order to see if the formulation maintains these cells in the epidermis.
  • the activity of the formulation is evaluated by visualization of the Langerhans cells after anti-CDla labeling. - - . . _- - .
  • the explants are treated by topical application of 4 mg of composition to be tested at the times
  • the sensitization phase is started by topical application of discs of filter paper 9 mm in diameter on which 25 ⁇ l of sensitizing composition have been previously deposited.
  • 3 sensitizers DCNB 0.0062%, nickel salt 0.1%, fragrance mix, Stallerpatch Diagnostic Epicutane from Stallergenes S. A
  • SDS 0.1%) an irritant product
  • explants from each batch are taken on D4, ie 24 hours after sensitization.
  • the explants taken are cut in half, one half is fixed in ordinary Bouin liquid while the other half is frozen at -80 ° C, for the different immunological markings.
  • Masson trichrome staining Langerhans cells appear as cells with clear cytoplasm in the epidermis; moreover, it is difficult to identify them in the dermis.
  • the ATPase reaction the reaction of ATP with the LC membrane makes it possible to visualize them in black-brown, but it is not specific for LCs.
  • the CL are CD positive in the epidermis and in the dermis. However, as they migrate, they become CDla negative, HLA-DR positive and CD36 positive.
  • the explants fixed in the Bouin are placed in a block, cut and staining with Masson trichrome is performed for the general morphological analysis.
  • the immunological labeling of Langerhans cells with anti-CDla is carried out on frozen sections cut with a cryostat.
  • Langerhans cells are quite numerous in the epidermis. Their dendricity is reduced. They are moderately present in the papillary dermis.
  • Anti-CD1 marking a The marked Langerhans cells are observed in the different layers of the epidermis, at the dermo-epidermal junction (JDE) and in the papillary and upper reticular dermis.
  • Langerhans cells are numerous, dendritic and well present in the various epidermal compartments. They are, by area, more or less present in the papillary dermis.
  • composition according to the invention In the presence of a composition according to the invention The general morphology is good and identical to that observed for the control on D0.
  • Langerhans cells are numerous with a good morphology. They are present in the various epidermal compartments and hardly visible in the papillary dermis.
  • the general morphology is good and identical to that observed for the control on D0.
  • Langerhans cells are few in the epidermis and often located near the JDE. Their dendricity is reduced.
  • the general morphology is good and identical to that observed for the control on D0.
  • Langerhans cells are few in the epidermis and their dendricity is reduced. They are clearly visible in the papillary dermis.
  • composition according to the invention induces a clear Langerhans cell protection activity with nickel nitrate, moderate with DNCB and slight with SDS.
  • the appended figures represent sections of epidermal and dermal tissue showing zones of more or less deep alteration after exposure to a solvent such as toluene (FIGS. 2A and 2B), to a surfactant such as 20% SDS, at a strong acid like hydrochloric acid and a strong base like 10% ammonia in comparison with the results obtained, with the irritant and with a composition according to the invention, as well as in comparison with a control and with the preparation according to the invention alone.
  • a solvent such as toluene
  • SDS surfactant
  • the objective of this study was to assess the protective activity of the barrier cream according to the invention against a very common allergen nickel, in the form of concentrated salt at 5% and 10% .
  • the visualization of the penetration of nickel nitrate was carried out by means of a specific coloration of sections of explants of human skin. The results showed that without protection, the nickel nitrate diffuses in the stratum corneum, all the more deeply as the contact times are high. Conversely, thanks to a pre-treatment with the barrier cream, the nickel nitrate remains strictly localized on the surface of the stratum cormneum and does not penetrate, whatever the allergen concentrations and the exposure time tested.
  • Nickel is a common allergen. It is one of the most common causes of allergic contact eczema (1, 2). The frequency of skin sensitization to nickel is constantly increasing. It concerns around 10% of the European population and women are mainly concerned (3). Nickel-induced allergic contact dermatitis of professional (4, 5) or domestic (6) origin often proves to be very disabling in everyday life and the elimination of the allergen remains a real problem. Thus, some professionals such as hairdressers (7) or mechanics (8) are particularly exposed to allergic contact dermatitis. These can also occur in contact with clothing (jeans buttons, belt buckle), glasses, costume jewelry, kitchen equipment or even coins. The ubiquity of nickel makes it crowded out difficult, hence the need to protect the seed coat to avoid recurrences. Gloves are often poorly supported, even incompatible with certain activities. Barrier creams therefore represent a promising therapeutic alternative. They appear to be effective and particularly well accepted, even in professional practice (9, 10).
  • the two 5% or 10% nickel nitrate solutions are applied to batches SI, S2, BS1 and BS2 using a filter paper disc impregnated with 25 ⁇ l of each solution. These discs remain in contact with the explants for 24 or 48 hours. Then 3 explants from each batch are removed and cut in half. Half an explant is frozen and stored at -80 ° C until freezing sections (5 ⁇ m) are produced, which are then stained according to the dimethylglyoxime method, specifically identifying nickel. The observations of the sections are then carried out under an optical microscope. The presence of nickel nitrate results in a pink-purple coloration developing after a few minutes of contact.
  • the barrier cream studied is a water-in-oil emulsion containing the active principle according to the invention.
  • This new active ingredient is a combination of two polymers:
  • phosphorylcholine polymer of biomimetic structure, this amphiphilic molecule integrates into the stratum corneum (SC) up to 10 ⁇ m deep and stabilizes the inter-corneocytic lamellar structures. This polymer has a high capacity for retaining water in the SC.
  • this is a protective active which acts on the surface by forming a network of meshes tight capable of trapping by ionic bonds irritants exogenous agents, such as heavy metals, dyes', solvents, detergents.
  • the explants treated with the barrier cream alone according to the invention are histologically similar to the untreated control explants: the laminated epidermis has a thick SC medium, well flaky and slightly keratinized at the base.
  • the application of the barrier cream does not modify the general morphology of the epidermis and confirms the absence of irritation of the product applied.
  • the pink coloration is strictly limited to the surface of the SC and does not diffuse.
  • the concentration gradient of the nickel adsorbed at the epidermal level varies according to the nature of the salt, the anatomical site, the dose and the exposure time. Thus, in the nitrate form, nickel penetrates beyond the SC, compared to other salts: chloride, sulfate or nickel acetate (14).
  • the results confirm the diffusion capacity of nickel nitrate in the SC: the allergen penetrates easily while respecting the morphology and structure of the epidermal layers. Regardless of the concentration used, nickel nitrate is detectable beyond the SC after 48 hours of contact. Conversely, on skin pretreated with the barrier cream according to the invention, the nickel nitrate remains strictly localized on the surface of the SC, whatever the concentrations and the contact times considered, and the explants are isolated and protected from the allergenic agent.
  • Example IV The present study confirms the protection results already obtained in Example IV and proves that it is possible to isolate the seed coat from the penetration of a sensitizing substance by applying a specific barrier cream.

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Abstract

The invention concerns the field of chemistry and more particularly the field of dermatology and/or cosmetics. More precisely, the invention concerns novel dermatological and/or cosmetologic compositions characterized in that they contain a combination of 2-vinylpyrrolidone homopolymer and n-butyl 2-methacryloxy ethylphosphorylcholine-methacrylate copolymer associated or mixed with one or several inert, non-toxic dermatologically acceptable carriers. The inventive formulations play an important role as skin restructuring agent to maintain skin integrity, as skin protector against allergies and skin irritation.

Description

NOUVELLES COMPOSITIONS DERMATOLOGIQUES ET/OU COSMETOLOGIQUES HYDRATANTES ET ANTI-IRRITANTES NEW HYDRATING AND ANTI-IRRITANT DERMATOLOGICAL AND / OR COSMETOLOGICAL COMPOSITIONS
La présente invention se rapporte au domaine de la chimie et plus particulièrement au domaine de la dermatologie et de la cosmétique.The present invention relates to the field of chemistry and more particularly to the field of dermatology and cosmetics.
Elle a plus précisément pour objet des compositions dermatologiques ou cosmétiques à action protectrice de surface ou réparatrice, à base de deux principes actifs qui contribuent à préserver l'homéostasie épidermique ou à la recouvrer.More specifically, it relates to dermatological or cosmetic compositions with protective surface or repairing action, based on two active principles which contribute to preserving or recovering epidermal homeostasis.
Elle concerne spécifiquement de nouvelles compositions dermatologiques et/ou cosmétiques destinées à exercer un effet de barrière contre les agents exogènes irritants ou allergisants et à jouer un rôle de protection cutanée, caractérisées en ce qu'elles contiennent comme principes actifs un homo polymère de N-vinyl 2-pyrrolidone" et un copolymère~de'2-méthacryloxy éthyl phosphoryl choline-méthacrylate de n-butyle associés à ou en mélange avec un ou plusieurs excipients ou véhicules inertes, non toxiques dermatologiquement acceptables.It specifically relates to new dermatological and / or cosmetic compositions intended to exert a barrier effect against irritating or allergenic exogenous agents and to play a skin protection role, characterized in that they contain as active principles a homopolymer of N- vinyl 2-pyrrolidone " and a copolymer ~ de'2-methacryloxy ethyl phosphoryl choline-n-butyl methacrylate associated with or in admixture with one or more excipients or inert, non-toxic dermatologically acceptable vehicles.
Le copolymère de 2-méthacryloyloxy éthylphosphoryl choline/méthacrylate de butyle a une structure similaire à celle du groupement polaire des phospholipides de la membrane cellulaire et en tant que tel il est parfaitement biocompatible.The copolymer of 2-methacryloyloxy ethylphosphoryl choline / butyl methacrylate has a structure similar to that of the polar group of phospholipids on the cell membrane and as such it is perfectly biocompatible.
Sa structure chimique estIts chemical structure is
X Y Ce copolymère dénommé PMPC se caractérise par la présence dans sa structure polymérisée, de branches de phospholipides polaires et peut s'intégrer en profondeur, jusqu'à une distance de lOμm, dans les structures lamellaires, organisées de manière similaire, de la barrière cutanée afin de les stabiliser, de les réparer ou de les reconstituer. Son action est tout à fait "bio-mimétique". Sa composition en fait un actif parfaitement "biocompatible". XY This copolymer called PMPC is characterized by the presence in its polymerized structure of branches of polar phospholipids and can be integrated in depth, up to a distance of 10 μm, into the lamellar structures, organized in a similar manner, of the skin barrier so stabilize, repair, or restore them. Its action is completely "bio-mimetic". Its composition makes it a perfectly "biocompatible" active ingredient.
Une fois intégré dans la barrière cutanée, le PMPC a également la capacité de retenir l'eau et de maintenir un taux idéal d'hydratation pour assurer une bonne plasticité de la couche cornée. Son pouvoir de rétention d'eau, comparé à celui de l'acide hyaluronique ou celui du pyrrolidone carboxylate de sodium, est supérieur à ces deux actifs hydratants de référence.Once integrated into the skin barrier, the PMPC also has the capacity to retain water and maintain an ideal rate of hydration to ensure good plasticity of the stratum corneum. Its water retention power, compared to that of hyaluronic acid or that of sodium pyrrolidone carboxylate, is superior to these two reference hydrating active ingredients.
Son effet sur la réduction de la Perspiration Insensible en Eau (PIE) a été démontrée ainsi que son effet bénéfique sur la viscoélasticité de la peau.Its effect on the reduction of Insensitive Water Perspiration (PIE) has been demonstrated as well as its beneficial effect on the viscoelasticity of the skin.
Le PMPC, à la surface de l'épiderme, a également un effet prononcé "anti-adhésion" vis-à-vis des protéines. Celles-ci étant souvent des molécules allergisantes, le PMPC pourrait donc protéger des allergies de contact, d'origine protéique.PMPC, on the surface of the epidermis, also has a pronounced "anti-adhesion" effect with respect to proteins. As these are often allergenic molecules, PMPC could therefore protect against contact allergies, of protein origin.
Une étude clinique a prouvé l'effet bénéfique de produits contenant du PMPC sur des dermatoses à peaux sèches, telles que des Xéroses, des Ichtyoses et de l'eczéma.A clinical study has proven the beneficial effect of products containing PMPC on dry skin dermatoses, such as Xerosis, Ichthyosis and eczema.
Enfin, le PMPC a montré son effet protecteur cutané vis-à-vis des irritations déclenchées par les Acides Alpha Hydroxy-carboxyliques (A.H.A.) comme l'acide glycolique ou l'acide lactique.Finally, the PMPC has shown its protective skin effect against irritations triggered by Alpha Hydroxy-carboxylic Acids (A.H.A.) such as glycolic acid or lactic acid.
Par ailleurs la polyvinyl pyrrolidone (PNP) joue un rôle très important en complément de l'action du PMPC. Elle agit principalement en formant un film non occlusif à la surface de la peau, physiologiquement inerte et d'une parfaite tolérance.In addition, polyvinyl pyrrolidone (PNP) plays a very important role in addition to the action of PMPC. It acts mainly by forming a non-occlusive film on the surface of the skin, physiologically inert and of perfect tolerance.
La Polyvinylpyrrolidone est définie chimiquement comme étant un homopolymère de Ν- Ninyl 2-pyrrolidone dont la formule est : Polyvinylpyrrolidone is defined chemically as being a homopolymer of Ν- Ninyl 2-pyrrolidone, the formula of which is:
Selon l'usage pour lequel cette substance est destinée, on utilise un homopolymère de N-Vinyl 2-pyrrolidone commercialisé sous les marques Plasdone K-25 (valeur de K = 24-26), Plasdone K-26/28, (K = 26-28), Plasdone K29/32 (K = 29-32), Plasdone K - 90 (K= 85-95) ou POVIDERM SK3.Depending on the use for which this substance is intended, use is made of a homopolymer of N-Vinyl 2-pyrrolidone sold under the brands Plasdone K-25 (value of K = 24-26), Plasdone K-26/28, (K = 26-28), Plasdone K29 / 32 (K = 29-32), Plasdone K - 90 (K = 85-95) or POVIDERM SK3.
Ce sont des produits très purs, stables, inodores et insipides, solubles dans l'eau et les systèmes de solvants organiques.They are very pure, stable, odorless and tasteless products, soluble in water and organic solvent systems.
Elle représente une nouvelle approche, utilisée pour réduire les problèmes de toxicité ou de sensibilisation déclenchés par des ingrédients chimiques.It represents a new approach, used to reduce toxicity or sensitization issues triggered by chemical ingredients.
La PNP est, par exemple, utilisée depuis longtemps en association avec l'iode afin de rendre l'utilisation de l'iode moins dangereuse, tout en conservant son activité antiseptique. La PNP prolonge également considérablement l'efficacité de certains actifs médicamenteux. Elle apporte une rémanence d'activité. On a aussi décrit son pouvoir protecteur des muqueuses vis-à-vis des toxines bactériennes.PNP has, for example, been used for a long time in combination with iodine in order to make the use of iodine less dangerous, while retaining its antiseptic activity. PNP also considerably prolongs the effectiveness of certain drug active ingredients. It brings a persistence of activity. We have also described its protective power of the mucous membranes against bacterial toxins.
Enfin, la PVP permet de réduire fortement les irritations et les sensibilisations induites par les Phénols, de diminuer les irritations déclenchées par les détergents et par les A.H.A. et de réduire la toxicité induite par le Formaldéhyde.Finally, PVP makes it possible to greatly reduce the irritations and sensitizations induced by phenols, to reduce the irritations triggered by detergents and by A.H.A. and reduce the toxicity induced by Formaldehyde.
En conséquence, le système selon l'invention est constitué d'une part, d'un polymère de Ninyl- Pyrrolidone (PNP) et d'autre part, d'un polymère de Phosphoryl Choline (PMPC) dans un excipient approprié.Consequently, the system according to the invention consists on the one hand, of a polymer of Ninyl-Pyrrolidone (PNP) and on the other hand, of a polymer of Phosphoryl Choline (PMPC) in a suitable excipient.
En conclusion le système associant le PMPC et la PNP n'est pas seulement un agent protecteur de surface, isolant la peau des agents exogènes irritants ou sensibilisants (allergènes protéiques, toxines bactériennes, détergents, acides, solvants, etc ..) mais aussi un système qui favorise la réparation par "biomimétisme" de la barrière cutanée et qui lui apporte une hydratation optimale qui lui permet de retrouver tout son équilibre.In conclusion, the system associating PMPC and PNP is not only a surface protective agent, isolating the skin from irritant or sensitizing exogenous agents. (protein allergens, bacterial toxins, detergents, acids, solvents, etc.) but also a system which promotes repair by "biomimicry" of the skin barrier and which provides it with optimal hydration which allows it to regain its balance.
La peau, répartie sur toute la surface corporelle, est tout d'abord un organe de protection des tissus sous-jacents, vis-à-vis d'agressions extérieures. Cette protection est assurée par une barrière physique particulièrement efficace, la couche cornée, couche la plus superficielle de l'épiderme. Elle est constituée d'un film hydro-lipidique de surface et de plusieurs couches de cellules mortes très kératinisées, les Cornéocytes. Ces cellules sont soudées entre elles par le ciment inter-cornéocytaire. Cet ensemble constitue un véritable mur "anti-agressions" et il est primordial de maintenir son intégrité.The skin, distributed over the entire body surface, is first of all a protective organ of the underlying tissues, against external aggressions. This protection is provided by a particularly effective physical barrier, the stratum corneum, the most superficial layer of the epidermis. It consists of a hydro-lipidic surface film and several layers of very keratinized dead cells, the Cornéocytes. These cells are welded together by inter-corneocytic cement. This set constitutes a real "anti-aggression" wall and it is essential to maintain its integrity.
Sous cette couche cornée, l'épiderme vivant assure d'une part la multiplication et la différenciation cellulaire qui permet de constituer une barrière cornée de bonne qualité et d'autre part des fonctions de protection active lorsque des stress extérieurs réussissent à passer au travers de la couche cornée. Par exemple, le rayonnement UV va stimuler la Mélanogénèse dont le but est d'absorber grâce à la mélanine, le plus possible de rayons UN pour éviter une altération des tissus vivants, épidermiques et dermiques.Under this stratum corneum, the living epidermis ensures on the one hand the cell multiplication and differentiation which makes it possible to constitute a good quality corneal barrier and on the other hand functions of active protection when external stresses manage to pass through the stratum corneum. For example, UV radiation will stimulate Melanogenesis, the purpose of which is to absorb, thanks to melanin, as much UN rays as possible to avoid damage to living, epidermal and dermal tissues.
D'autre part, le passage de corps étrangers peut activer les cellules de Langerhans, cellules "sentinelles" de l'épiderme, qui en migrant vers le derme vont stimuler la réaction inflammatoire, réaction de défense de la peau pour se débarrasser de ces substances étrangères.On the other hand, the passage of foreign bodies can activate the cells of Langerhans, "sentinel" cells of the epidermis, which by migrating towards the dermis will stimulate the inflammatory reaction, defense reaction of the skin to get rid of these substances. Foreign.
L'épiderme peut également libérer des "défensines" sous l'influence d'agressions , toujours pour se protéger.The epidermis can also release "defensins" under the influence of aggressions, always to protect itself.
Il va de soi que ces différents systèmes de protection ne doivent pas être hyper-stimulés par des agressions trop répétitives sous peine de voir leur capital de protection s'épuiser. C'est ce qui se passe pour la mélanogénèse ou pour les défensines. Une hyper-stimulation peut également évoluer vers des réactions inflammatoires chroniques difficiles à enrayer et devenant néfastes pour la peau.It goes without saying that these different protection systems must not be hyper-stimulated by too repetitive aggressions, otherwise their protection capital will run out. This is what happens for melanogenesis or for defensins. Hyper-stimulation can also progress to chronic inflammatory reactions which are difficult to control and which are harmful for the skin.
C'est pourquoi pour préserver ou économiser les fonctions de défense "actives" de la peau, la barrière cornée de surface doit être parfaitement constituée. Le système de double protection active, est une association originale de deux substances, l'une agissant en surface, la deuxième agissant dans la profondeur de la couche cornée.This is why to preserve or save the "active" defense functions of the skin, the surface corneal barrier must be perfectly formed. The active double protection system is an original association of two substances, one acting on the surface, the second acting in the depth of the stratum corneum.
On peut donc considérer que le système objet de la présente invention, contribue à assurer la préservation de l'Homéostasie épidermique, pour le moins à un retour à cet état d'équilibre fragile.It can therefore be considered that the system which is the subject of the present invention contributes to ensuring the preservation of epidermal homeostasis, at least to a return to this fragile state of equilibrium.
Selon la présente invention l'excipient est un agent diluant, minéral ou organique, un agent de charge minéral ou organique, un agent liant, un agent d'écoulement ou un agent donnant l'éclat nacré.According to the present invention, the excipient is a diluent, mineral or organic agent, a mineral or organic filler, a binding agent, a flow agent or an agent giving the pearly luster.
Un véhicule est un mélange liquide, pâteux ou visqueux qui permet le transport de la préparation au contact de la peau, des téguments ou des muqueuses. Le véhicule pourra être de l'eau ou un liquide aqueux, un produit huileux, une silicone et/ou un solvant organique.A vehicle is a liquid, pasty or viscous mixture which allows the transport of the preparation in contact with the skin, the integuments or the mucous membranes. The vehicle may be water or an aqueous liquid, an oily product, a silicone and / or an organic solvent.
Parmi les compositions liquides ou fluides, objet de la présente invention, on pourra citer les crèmes, les pommades, les gels anhydrides ou aqueux, les lotions, les émulsions H/E ou E/H, les pains, les savons, les laits pour la douche et similaires.Among the liquid or fluid compositions which are the subject of the present invention, mention may be made of creams, ointments, anhydrous or aqueous gels, lotions, O / W or W / O emulsions, breads, soaps, milks for shower and the like.
Les compositions selon l'invention contiennent de 0,1 à 4 % de polyvinyl pyrrolidone avec une préférence à 1,5 à 2,5 %. La PMPC se trouve présente dans les compositions en une quantité s'échelonnant de 0,1 à 4 % par rapport à la composition totale, avec une préférence de l'ordre de 1,8 à 2,5 %.The compositions according to the invention contain 0.1 to 4% of polyvinyl pyrrolidone with preferably 1.5 to 2.5%. PMPC is present in the compositions in an amount ranging from 0.1 to 4% relative to the total composition, with a preference of the order of 1.8 to 2.5%.
Les compositions selon l'invention peuvent également renfermer des silicones qui améliorent la stabilité des émulsions et assurent une sensation de douceur pour la peau lors de l'application, des agents épaississants, des agents diluants, des agents de pénétration, des agents aromatisants et/ou des agents conservateurs.The compositions according to the invention may also contain silicones which improve the stability of the emulsions and ensure a feeling of softness for the skin during application, thickening agents, diluents, penetration agents, flavoring agents and / or preservatives.
Parmi les agents épaississants on pourra citer les gommes naturelles ou synthétiques, les dérivés de la cellulose, les argiles gonflantes du type Bentone, des polymères d'acide acrylique, des polymères d'amide acrylique, des N-alkyl (polyhydroxyl akyl) glucuronamides, les amidons, les amidons modifiés, les polysaccharides, les dextrinës, les silicates lamellaires et les produits similaires. Parmi les agents diluants on pourra citer des sels minéraux insolubles ou peu solubles dans l'eau tels que des carbonates de métal alcalino-terreux, de magnésium ou de zinc, des titanates de métal alcalin ou de métal alcalino-terreux, du dioxyde de titane, des oxydes métalliques comme des oxydes de fer, de l'oxyde de zinc, de l'oxyde d'étain, des sulfates de métal alcalino-terreux comme le sulfate de calcium ou le sulfate de baryum, des phosphates mono-, di-ou tri-basiques comme l'hydrogéno phosphate de calcium, le phosphate tricalcique ou le phosphate de magnésium.Among the thickening agents, mention may be made of natural or synthetic gums, cellulose derivatives, swelling clays of the Bentone type, acrylic acid polymers, acrylic amide polymers, N-alkyl (polyhydroxyl akyl) glucuronamides, starches, modified starches, polysaccharides, dextrins, lamellar silicates and the like. Among the diluents, mention may be made of mineral salts which are insoluble or poorly soluble in water, such as alkaline earth metal carbonates, magnesium or zinc, alkali metal or alkaline earth metal titanates, titanium dioxide , metal oxides such as iron oxides, zinc oxide, tin oxide, alkaline earth metal sulfates such as calcium sulfate or barium sulfate, mono-, di- or tri-basic like calcium hydrogen phosphate, tricalcium phosphate or magnesium phosphate.
Parmi les agents de pénétration on pourra citer les lactames aliphatiques comme le caprolactame, des acides gras comme l'acide oléique, des alcools gras comme l'alcool laurique ou l'alcool pélargomique ou des dérivés du dioxolane comme le diméthyl dioxolane ou le méthylnonyldioxolane.Among the penetration agents, mention may be made of aliphatic lactams such as caprolactam, fatty acids such as oleic acid, fatty alcohols such as lauric alcohol or pelargomic alcohol or dioxolane derivatives such as dimethyl dioxolane or methylnonyldioxolane.
L'agent d'aromatisation pourra être une essence ou une huile essentielle ou un concentré de parfum, obtenu à partie des feuilles, des fleurs, des bourgeons, des racines ou des écorces de plantes odoriférantes. On pourra également utiliser un ou plusieurs des constituants de ces essence obtenus par distillation, séparation, par chromatographie ou bien encore par synthèse. Des produits aromatisants avantageux sont par exemple l'aldéhyde benzoïque, l'aldéhyde cinnamique, l'eugenol, le cinéol ou le lavandinol. On pourra également utiliser avantageusement l'essence de géranium rosat, l'essence de lavandin, l'essence de lavande, l'essence de lemon-grass, l'essence de mandarine, l'essence de néroli, l'essence de petit grain, le patchouli ou l'Ylang-Ylang, seuls ou en mélange.The flavoring agent may be an essence or an essential oil or a perfume concentrate, obtained from the leaves, flowers, buds, roots or barks of odorous plants. It is also possible to use one or more of the constituents of these essences obtained by distillation, separation, by chromatography or even by synthesis. Advantageous flavoring products are, for example, benzoic aldehyde, cinnamic aldehyde, eugenol, cineol or lavandinol. We can also advantageously use the essence of geranium rosat, the essence of lavandin, the essence of lavender, the essence of lemon grass, the essence of mandarin, the essence of neroli, the essence of petit grain , patchouli or Ylang-Ylang, alone or as a mixture.
Les compositions liquides seront additionnées d'un ou plusieurs agents conservateurs parmi lesquels les esters d'acide p-hydroxybenzoïque, les esters d'acide salicylique, l'acide sorbique, les dérivés de l'urée, les phénols, l'acide coumarique ou l'alcool benzylique.The liquid compositions will be added with one or more preserving agents among which the esters of p-hydroxybenzoic acid, the esters of salicylic acid, sorbic acid, derivatives of urea, phenols, coumaric acid or benzyl alcohol.
Les compositions dermatologiques et/ou cosmétiques selon l'invention, sont préparées selon des procédés usuels en cosmétologie par mélange, par broyage ou par fusion des principes actifs et incorporation à un excipient ou à un véhicule puis aromatisation et répartition dans des emballages ou des flaconnages de forme ou de volume approprié.The dermatological and / or cosmetic compositions according to the invention are prepared according to methods customary in cosmetology by mixing, by grinding or by fusion of the active principles and incorporation into an excipient or a vehicle then aromatization and distribution in packaging or bottles. of appropriate shape or volume.
Les compositions selon l'invention trouvent un emploi comme protecteur cutané en maintenant l'intégrité de la peau et en exerçant un effet barrière, un emploi comme restructurant de la peau et des muqueuses après destruction, notamment par lésion professionnelle, comme agent anti-allergie contre les irritations, les macérations et encore contre l'hyper stimulation, dans le traitement des dermites et notamment des dermites orthoergiques. Les compositions selon l'invention trouvent une utilisation plus particulière pour la prévention et le traitement des allergies cutanées dues au nickel, notamment aux bijoux contenant du nickel.The compositions according to the invention find use as a skin protector by maintaining the integrity of the skin and by exerting a barrier effect, use as restructuring of the skin and mucous membranes after destruction, in particular by occupational injury, as an anti-allergy agent against irritation, maceration and also against hyper stimulation, in the treatment of dermatitis and in particular orthoergic dermatitis. The compositions according to the invention find a more particular use for the prevention and the treatment of skin allergies due to nickel, in particular to jewelry containing nickel.
Les compositions sont destinées à être appliquées sur la peau, les muqueuses ou les téguments de 1 à 4 fois par jour notamment sous forme de poudres, de lait, de crème ou d'émulsion.The compositions are intended to be applied to the skin, the mucous membranes or the integuments from 1 to 4 times a day, in particular in the form of powders, milk, cream or emulsion.
Les exemples suivants illustrent l'invention sans toutefois la limiter.The following examples illustrate the invention without, however, limiting it.
EXEMPLE IEXAMPLE I
Crème PMPC 0,1 % en poidsPMPC cream 0.1% by weight
Polyvinyl pyrrolidone 4,0 %Polyvinyl pyrrolidone 4.0%
Polydécène 15 % Agent tensioactif non ionique commercialisé sous la marque Arlacel PI 35 1 %Polydecene 15% Non-ionic surfactant sold under the brand name Arlacel PI 35 1%
Perhydrosqualène 0,5 % Glycérol 4 %Perhydrosqualene 0.5% Glycerol 4%
Phenonip 0,2 %0.2% Phenonip
Huile d'amandes douces 15 % Eau purifiée qsp 100gSweet almond oil 15% Purified water qs 100g
EXEMPLE IIEXAMPLE II
LotionLotion
PMPC 3 %PMPC 3%
Polyvinyl pyrrolidone . 0,5 %Polyvinyl pyrrolidone. 0.5%
Squalane • 2 % Cholestérol 1 %Squalane • 2% Cholesterol 1%
Poly éthylène glycol 400 5 %Poly ethylene glycol 400 5%
Phenonip 0,2 %0.2% Phenonip
Polysorbate 80 0,5 %Polysorbate 80 0.5%
Huile de ricin hydrogénée 1 % Essence de Lavandin 0,2 %1% hydrogenated castor oil Lavandin essence 0.2%
Eau qsp 100 gWater qs 100 g
EXEMPLE III LaitEXAMPLE III Milk
PMPC 2 %PMPC 2%
Polyvinyl pyrrolidone 2 %Polyvinyl pyrrolidone 2%
Dioxyde de titane micronisé 0,1 %0.1% micronized titanium dioxide
Alcool cétylique 3 % Propylène glycol 6 %Cetyl alcohol 3% Propylene glycol 6%
Agent conservateur 0,15 %Preservative 0.15%
Parfum floral 0,15 % Eau qsp 100 gFloral fragrance 0.15% Water qs 100 g
EXEMPLE IVEXAMPLE IV
GelGel
PMPC 2 %PMPC 2%
Polyvinyl pyrrolidone 2 %Polyvinyl pyrrolidone 2%
Glycérol * 6 % Triéthanolamine 0,1 %Glycerol * 6% Triethanolamine 0.1%
Carbomère (Carbopol 941 de la société Goodrich) 0,5 %Carbomer (Carbopol 941 from Goodrich) 0.5%
Cyclométhicone 0,5 %Cyclomethicone 0.5%
Extrait de lavande 0,15 %Lavender extract 0.15%
Eau déminéralisée qsp 100 gDemineralized water qs 100 g
EXEMPLE NEXAMPLE N
Evaluation de l'action anti-irritante d'une composition selon l'invention vis-à-vis des différentes agressions extérieures (détergents, acides, bases, solvants organiques).Evaluation of the anti-irritant action of a composition according to the invention with regard to the various external aggressions (detergents, acids, bases, organic solvents).
Le but de cette étude est de déterminer le potentiel anti-irritant de la composition selon l'invention sur des explants de peau humaine maintenus en survie, vis à vis des agressions extérieures provoquées par l'application de différents produits chimiques; irritants ou caustiques, comme le lauryl sulfate de sodium, l'acide chlorhydrique, Fair-moniaque et le toluène. 1 - Préparation des explantsThe purpose of this study is to determine the anti-irritant potential of the composition according to the invention on explants of human skin maintained in survival, with respect to external aggressions caused by the application of different chemicals; irritants or caustics, such as sodium lauryl sulphate, hydrochloric acid, Fair-moniac and toluene. 1 - Preparation of explants
33 explants, de peau humaine (diamètre 1cm) sont découpés à l'aide d'un bistouri emporte- pièce sur des plasties provenant de cliirurgie plastique. Ils sont mis en survie dans des boites de culture à 6 puits avec du milieu BEM (BIO-EC's Explants Médium) selon la procédure décrite dans la littérature.33 explants, of human skin (diameter 1cm) are cut using a puncture knife on plasties from plastic surgery. They are put into survival in 6-well culture dishes with BEM medium (BIO-EC's Explants Medium) according to the procedure described in the literature.
Répartition des 33 explants PI 73 -MB 36 en 10 lots de 3 + 3 Témoin T0Distribution of the 33 explants PI 73 -MB 36 into 10 lots of 3 + 3 T0 control
2 - Traitement2 - Treatment
La composition selon l'invention est appliquée à raison de 2 mg/ cm2 (2μl) par explant, répartie à l'aide d'un doigtier stérile. L'application est renouvelée 10 min après séchage complet du produit. Le produit est appliqué en deux couches successives et représente une quantité totale de 4 mg/cm .The composition according to the invention is applied at a rate of 2 mg / cm 2 ( 2 μl) per explant, distributed using a sterile finger pad. The application is repeated 10 min after complete drying of the product. The product is applied in two successive layers and represents a total amount of 4 mg / cm.
3 -Adressions3 - Addresses
Les explants sont placés dans du HBSS (nouvelles plaques à 6 puits).The explants are placed in HBSS (new 6-well plates).
L'agression par les produits irritants est réalisée par application topique de disque de papier filtre de 6 mm de diamètre sur lesquels 15 μl de produit ont été préalablement déposés.Aggression by irritants is carried out by topical application of a 6 mm diameter filter paper disc on which 15 μl of product have been previously deposited.
4 - Prélèvements 2 heures après l'application des produits irritants :4 - Direct debits 2 hours after applying the irritants:
- Prélèvement des 3 explants de chaque lot et fixation au liquide de Bouin.- Collection of the 3 explants from each batch and fixation with Bouin's liquid.
- Prélèvement du HBSS (2ml), 1 ml est congelé en vue du dosage des PGE2 et 1 ml est directement utilisé pour le dosage de LDH.- HBSS sample (2ml), 1 ml is frozen for the assay of PGE2 and 1 ml is used directly for the assay of LDH.
5 - Etude histologique5 - Histological study
A partir des explants fixés au liquide de Bouin ordinaire, après imprégnation en paraffine, mise en bloc, coupes à 5μm et montage, une coloration au trichrome de Masson est réalisée.From the explants fixed to the ordinary Bouin liquid, after impregnation with paraffin, blocking, sections at 5 μm and mounting, staining with Masson trichrome is carried out.
6 -Dosage de la PGE2 6 - Dose of PGE 2
La PGE2 est dosée dans les milieux de culture prélevés après deux heures de_contact avec les agents agresseurs, par une méthode immuno-enzymatique (kit de Dosage EIA R&D).PGE 2 is assayed in the culture media taken after two hours of contact with the attacking agents, by an immunoenzymatic method (EIA R&D assay kit).
7- Dosage de LDH7- LDH dosage
La LDH est dosée dans les milieux de culture prélevés à J4, par une méthode immuno- enzymatique.The LDH is assayed in the culture media taken on D4, by an immunoenzymatic method.
RESULTATS 1 -Etude morphologiqueRESULTS 1 - Morphological study
I- Peau témoin : Structure épidermique normale avec un stratum corneum feuilleté et faiblement kératinisé.I- Control skin: Normal epidermal structure with a laminated and weakly keratinized stratum corneum.
II- Peau traitée avec la composition selon l'invention structure épidermique normale avec un stratum corneum légèrement feuilleté et faiblement kératinisé en basale.II- Skin treated with the composition according to the invention normal epidermal structure with a slightly laminated stratum corneum and weakly keratinized at the basal level.
III- Peau traitée avec la solution de SDS à 20% : Structure épidermique normale , avec un stratum corneum assez compact, très kératinisé en surface et légèrement kératinisé en basale. IV- Peau traitée avec la composition selon l'invention + SDS à 20% : Structure épidermique normale avec un stratum corneum légèrement plus compact, très kératinisé en surface et légèrement kératinisé en basale.III- Skin treated with the 20% SDS solution: Normal epidermal structure, with a fairly compact stratum corneum, very keratinized on the surface and slightly keratinized on the basal. IV- Skin treated with the composition according to the invention + SDS at 20%: Normal epidermal structure with a slightly more compact stratum corneum, very keratinized on the surface and slightly keratinized on the basal.
V- Peau traitée avec la solution de HC1 à 10%> : Structure épidermique montrant quelques zones d'altérations. Stratum corneum légèrement compact et nettement kératinisé' en basale.V- Skin treated with 10% HC1 solution>: Epidermal structure showing some areas of alteration. Stratum corneum slightly compact and clearly keratinized 'at the basal level.
VI Peau traitée avec la composition selon l'invention + HC1 à 10% : Stratum corneum très feuilleté légèrement kératinisé en surface et nettement kératinisé en basale.VI Skin treated with the composition according to the invention + HC1 at 10%: very laminated stratum corneum slightly keratinized on the surface and clearly keratinized on the basal.
VI- Peau traitée avec la solution de NH OH à 10%> : Stratum corneum compact et légèrement kératinisé en surface et en basale. Structure épidermique montrant quelques zones d'altérations.VI- Skin treated with 10% NH OH solution>: Stratum corneum compact and slightly keratinized on the surface and basal. Epidermal structure showing some areas of alteration.
VII Peau traitée avec la composition selon l'invention + NH OH à 10% : Structure épidermique normale avec un stratum corneum très feuilleté et kératinisé en basale.VII Skin treated with the composition according to the invention + NH OH at 10%: Normal epidermal structure with a very laminated and keratinized stratum corneum at the basal level.
VII- Peau traitée avec la solution de Toluène pur : Stratum corneum compact, plus ou moins kératinisé en surface et en basale. Structure épidermique montrant de fortes altérations cellulaires.VII- Skin treated with pure Toluene solution: compact Stratum corneum, more or less keratinized on the surface and basal. Epidermal structure showing strong cellular alterations.
VIII- Peau traitée avec la composition selon l'invention + Toluène : Stratum corneum compact, nettement kératinisé en surface et en basale. Structure épidermique montrant de fortes altérations cellulaires.VIII- Skin treated with the composition according to the invention + Toluene: Compact stratum corneum, markedly keratinized at the surface and at the base. Epidermal structure showing strong cellular alterations.
2 - Résultats du dosage de la PGE2 (voir figure 6) Le dosage est réalisé à l'aide d'un kit de dosage ELIS A R&D et les résultats sont exprimés en pg de PGE2/ml de milieu.2 - Results of the PGE2 assay (see FIG. 6) The assay is carried out using an ELIS A R&D assay kit and the results are expressed in pg of PGE2 / ml of medium.
3 - Résultats du dosage de la LDH (voir figure 7) La LDH est dosée dans les milieux de culture prélevés à J4, par une méthode immuno- enzymatique.3 - Results of the LDH assay (see Figure 7) The LDH is assayed in the culture media taken on D4, by an immunoenzymatic method.
DISCUSSIONDISCUSSION
1 -Observations morphologiques1 - Morphological observations
La composition selon l'invention diminue l'activité du SDS action en montrant un stratum corneum moins compact et moins kératinisé. L'application du produit au même temps qu'une solution de HCl à 10%>, améliore l'aspect du stratum corneum (feuilleté et moins kératinisé ). Cette amélioration est identique en présence d'ammoniaque.The composition according to the invention reduces the activity of the SDS action by showing a less compact and less keratinized stratum corneum. Applying the product at the same time as a 10% HCl solution> improves the appearance of the stratum corneum (laminated and less keratinized). This improvement is identical in the presence of ammonia.
En revanche, la présence du produit avec le toluène ne limite pas les altérations causées par ce dernier.On the other hand, the presence of the product with toluene does not limit the alterations caused by the latter.
2 -Dosage des PGE2 - La composition selon l'invention seule n'entraîne pas de modifications significatives du taux de PEG2. 2 - Dosage of PGE2 - The composition according to the invention alone does not cause significant changes in the level of PEG 2.
- Une application préventive de la composition selon l'invention entraîne une diminution significative du taux de PEG2 induit par l'application du SDS à 20 %,- A preventive application of the composition according to the invention leads to a significant reduction in the level of PEG 2 induced by the application of SDS to 20%,
- Une application préventive de la composition selon l'invention n'entraîne pas une diminution significative du taux de PEG2 induit par l'application d'une solution de- A preventive application of the composition according to the invention does not lead to a significant reduction in the level of PEG 2 induced by the application of a solution of
HCl à 10 % ou de SDS à 20 %,10% HCl or 20% SDS,
- Une application préventive de la composition selon l'invention entraîne une diminution significative du taux de PEG induit par l'application d'une solution d'ammoniaque à 10 %, - Une application préventive de la composition selon l'invention entraîne une diminution significative du taux de PEG2 induit par l'application de toluène pur.- A preventive application of the composition according to the invention results in a significant reduction in the level of PEG induced by the application of a 10% ammonia solution, - A preventive application of the composition according to the invention results in a significant reduction the level of PEG 2 induced by the application of pure toluene.
3- Dosage des LDH3- Determination of LDH
L'application du produit selon l'invention n'induit pas une diminution significative de taux de la LDH avec la solution de HCl à 10 %, du SDS à 20 % et d'une solution de NH4OH. En revanche son application avec le toluène pur induit une diminution significative de l'ordre d'environ 20 %.The application of the product according to the invention does not induce a significant reduction in the LDH level with the 10% HCl solution, the 20% SDS and a NH 4 OH solution. On the other hand, its application with pure toluene induces a significant reduction of the order of about 20%.
Dans ces conditions opératoires et en se basant sur les variation de taux de la LDH et de PGE2 la présence de composition selon l'invention permet de noter que le produit induit une protection significative vis à vis de NH4OH à 10 %>, de SDS à 20 %> et de toluène pur.Under these operating conditions and based on the variation in LDH and PGE2 levels, the presence of composition according to the invention makes it possible to note that the product induces significant protection with respect to NH4OH at 10%>, from SDS to 20%> and pure toluene.
En basant sur les variation de taux de la LDH en présence du produit selon l'invention , on peut conclure que le produit induit une protection significative seulement vis à vis du toluène pur.Based on the variations in LDH level in the presence of the product according to the invention, it can be concluded that the product induces significant protection only with respect to pure toluene.
Les observations morphologiques montrent que les compositions selon l'invention induisent une protection vis à vis des agressions apportées par SDS à 20 %, par NH4OH à 10 % et par HCl à l0 %.Morphological observations show that the compositions according to the invention induce protection against aggressions brought by SDS at 20%, by NH4OH at 10% and by HCl at 10%.
EXEMPLE VIEXAMPLE VI
Evaluation de l'activité protectrice des compositions selon l'invention vis-à-vis de l'allergie de contactEvaluation of the protective activity of the compositions according to the invention with respect to contact allergy
INTRODUCTIONINTRODUCTION
L'hypersensibilité de contact (ou allergie de contact ) est un problème de santé important dans la plupart des pays industrialisés. Les allergènes les plus rencontrés sont les constituants des parfums et des cosmétiques, les topiques médicamenteux, les produits de nettoyage, les produits dentaires, les produits de laboratoires et bien d'autres.Contact hypersensitivity (or contact allergy) is a major health problem in most industrialized countries. The most encountered allergens are the constituents of perfumes and cosmetics, topical drugs, cleaning products, dental products, laboratory products and many others.
On distingue deux phases dans ce processus d'allergie de contact :There are two phases in this process of contact allergy:
1 - Phase de sensibilisation1 - Awareness phase
Les haptènes sont des molécules chimiques de faible poids moléculaire capables d' interagir avec des acides aminés présents sur des protéines extracellulaires, membranaires ou intracellulaire. Quand l'haptène pénètre dans l'épiderme, il est fixé par des liaisons de haute affinité à des molécules porteuses, puis il est pris en charge par les cellules de Langerhans (latence). Cette phase de latence entraîne la synthèse de récepteurs membranaires : les molécules du CMH de classe I et de classe II (Complexe Majeur d'Histocompatibilité). Cette étape est accompagnée de l'activation des cellules de Langerhans (CL) avec production de cytokines. Puis, les CL migrent jusqu'aux ganglions entraînant l'expansion clonale des lymphocytes T (LT) qui se répartissent ensuite dans les différents tissus de l'organisme.Haptens are low molecular weight chemical molecules capable of interacting with amino acids present on extracellular, membrane or intracellular proteins. When hapten enters the epidermis, it is attached by high affinity bonds to carrier molecules, then it is taken up by Langerhans cells (latency). This latency phase leads to the synthesis of membrane receptors: MHC class I and class II molecules (Major Histocompatibility Complex). This step is accompanied by the activation of Langerhans cells (CL) with production of cytokines. Then, the CL migrate to the nodes causing the clonal expansion of T lymphocytes (LT) which are then distributed in the various tissues of the body.
2 -Phase de révélation2 -Phase of revelation
Lors des contacts ultérieurs avec l'haptène, celui-ci diffuse dans l'épiderme. Les CL hapténisées migrent dans le derme où elles vont présenter l'haptène en association avec les molécules du CMH I et II, aux LT mémoires présents dans le derme. Il y a alors activation lymphocytaire, production de cytokines Thl, ce qui aboutit à l'activation d'autres types cellulaires dont les cellules endothéliales et les kératinocytes. Ceci provoque une réaction de type allergie.During subsequent contact with hapten, it diffuses into the epidermis. The haptenized CL migrate in the dermis where they will present the hapten in association with the molecules of the MHC I and II, to the LT memories present in the dermis. There is then lymphocyte activation, production of Th1 cytokines, which leads to the activation of other cell types including endothelial cells and keratinocytes. This causes an allergy-like reaction.
Les cellules de Langerhans (CL) appartiennent à la famille des cellules dendritiques qui sont caractérisées essentiellement par leur forme, leur capacité à induire une réponse immune primaire, leur expression élevée de CMH II et leur mobilité. Elles sont issues de la différenciation des cellules souche de la moelle osseuse. Les CL assurent la surveillance immunitaire de la peau et contiennent des structures spécifiques intracytoplasmiques appelées granules de Birbeck. Enfin, elles présentent entre autres l'anti-gène CD la très abondant sur leur membrane.Langerhans cells (CL) belong to the family of dendritic cells which are essentially characterized by their shape, their ability to induce a primary immune response, their high expression of MHC II and their mobility. They arise from the differentiation of stem cells from the bone marrow. LCs provide immune surveillance for the skin and contain specific intracytoplasmic structures called Birbeck granules. Finally, they present, among other things, the very abundant CD anti-gene on their membrane.
Après captation de l'haptène, les CL migrent jusqu'aux ganglions lymphatiques via les vaisseaux lymphatiques. Au cours de leur déplacement, ces cellules subissent des modifications phénotypiques : en effet, elles sont CD la positives dans le derme et l'épiderme, mais au fur et à mesure de leur migration elles deviennent CD la négatives et expriment alors d'autres antigènes (tels que HLA-DR et CD36). Elles subissent également des modifications morphologiques (cellules de morphologie dendritique dans l'épiderme, plus arrondies dans le derme, voilées dans les canaux lymphatiques) et des modifications fonctionnelles (perte de la fonction d'apprêtement, acquisition de la fonction de présentation et d'activation lymphocytaire). Dans les ganglions, elles présentent les antigènes aux lymphocytes T naïfs et induisent ainsi une réponse immune primaire spécifique. Il existe donc une circulation des CL selon les conditions immunologiques.After capturing the hapten, the LCs migrate to the lymph nodes via the lymphatic vessels. During their movement, these cells undergo phenotypic changes: in fact, they are CD positive in the dermis and epidermis, but as they migrate they become CD negative and then express other antigens (such as HLA-DR and CD36). They also undergo morphological modifications (cells of dendritic morphology in the epidermis, more rounded in the dermis, veiled in the lymphatic channels) and functional modifications (loss of the function of dressing, acquisition of the function of presentation and lymphocyte activation). In the ganglia, they present the antigens to naive T lymphocytes and thus induce a specific primary immune response. There is therefore a circulation of CL according to the immunological conditions.
Migration des CL vers les ganglionsCL migration to the lymph nodes
Deux événements essentiels interviennent dans cette migration : le signal, puis la mobilité engendrée par ce signal.Two essential events intervene in this migration: the signal, then the mobility generated by this signal.
1- Les signaux Plusieurs types de signaux favorisent la migration des CL épidermiques ( mise en évidence essentiellement sur la souris) :1- Signals Several types of signals favor the migration of epidermal LCs (highlighted mainly on the mouse):
- Le contact avec des haptènes forts : TNCB, DNCB, DNFB, FITC...- Contact with strong haptens: TNCB, DNCB, DNFB, FITC ...
- L'irradiation par des rayons ultraviolets : UVB .- Ultraviolet rays irradiation: UVB.
- Différentes cytokines : ILlβ, TNFα, GM-CSF.... - Les molécules intervenant dans la signalisation cellulaire : les protéines kinases C .- Different cytokines: ILlβ, TNFα, GM-CSF .... - The molecules involved in cell signaling: protein kinases C.
- La chimiokine MIP-3β qui attire les CL hors de l'épiderme- The chemokine MIP-3β which attracts CL from the epidermis
En revanche, des interleukines comme IL4 et IL 10 inhibent la migration des CL .In contrast, interleukins like IL4 and IL 10 inhibit the migration of CL.
2- La mobilité De nombreuses interactions entre les cellules et la matrice extracellulaire sont à l'origine de la mobilité des CL.2- Mobility Many interactions between cells and the extracellular matrix are at the origin of LC mobility.
Au sein de l'épiderme, la E-cadhérine (molécule appartenant à la famille des molécules d'adhérence) relie les CL aux kératinocytes. Chez la souris, il a été démontré que les signaux donnés d'une part par les cytokines et d'autre part par un haptène diminuaient l'expression de la E-cadhérine. Ainsi, les CL se « détachent » des kératinocytes et peuvent migrer jusqu'aux ganglions).Within the epidermis, E-cadherin (a molecule belonging to the family of adhesion molecules) connects LCs to keratinocytes. In mice, the signals given on the one hand by cytokines and on the other hand by a hapten have been shown to decrease the expression of E-cadherin. Thus, LCs "detach" from keratinocytes and can migrate to the lymph nodes).
Etude de la migration des CLCL migration study
Modèle ex-vivo : explants Le principe est basé sur l'utilisation de biopsies de peau humaine, obtenues à partir de chirurgie plastique. Les substances à tester sont appliquées directement sur la peau qui est maintenue à 37°C . Des coupes de peau (épaisseur de 5 μm) sont alors effectuées afin d'observer, après marquage avec des anticorps spécifiques (anti-CDla, anti- HLA-DR), les cellules de Langerhans. Une diminution significative du nombre de CL résiduelles dans l'épiderme est observée après l'application d'haptènes forts alors que ces changements ne sont pas observés après application de substances irritantes .Ex-vivo model: explants The principle is based on the use of human skin biopsies, obtained from plastic surgery. The test substances are applied directly to the skin which is maintained at 37 ° C. Skin sections (thickness of 5 μm) are then made in order to observe, after labeling with specific antibodies (anti-CDla, anti-HLA-DR), the Langerhans cells. A significant decrease in the number of residual LCs in the epidermis is observed after the application of strong haptens while these changes are not observed after application of irritant substances.
ETUDE DE L'ALLERGIE DE CONTACT Cette étude a pour but de mettre en évidence l'activité d'une formulation selon l'invention vis à vis de l'allergie de contact.STUDY OF CONTACT ALLERGY The aim of this study is to demonstrate the activity of a formulation according to the invention with respect to contact allergy.
L'étude est menée pour déterminer l'activité de la formulation vis à vis de la sensibilisation de contact. Les explants sont prétraités pendant 48h par la formulation, puis des allergisants de référence sont appliqués afin de voir si la formulation maintient ces cellules dans l'épiderme.The study is conducted to determine the activity of the formulation with respect to contact awareness. The explants are pretreated for 48 hours with the formulation, then reference allergens are applied in order to see if the formulation maintains these cells in the epidermis.
L'activité de la formulation est évaluée par visualisation des cellules de Langerhans après marquage anti-CDla. - -. . _- - . The activity of the formulation is evaluated by visualization of the Langerhans cells after anti-CDla labeling. - - . . _- - .
MODE OPERATOIREOPERATING MODE
/ -Préparation des explants/ -Preparation of explants
On prépare 33 explants de peau humaine et on les met en survie en milieu BEM (BIO-EC's33 explants of human skin are prepared and they are put to survival in a BEM environment (BIO-EC's
Explants Médium).Explants Medium).
Répartition des explants en 10 lots de 3 explants et un lot de trois explants comme témoin T0.Distribution of the explants into 10 lots of 3 explants and a lot of three explants as control T0.
2 - Traitement2 - Treatment
Les explants sont traités par application topique de 4 mg de composition à tester aux tempsThe explants are treated by topical application of 4 mg of composition to be tested at the times
J0, Jl et J2 ( application le soir ) Les lots non-traités ne reçoivent aucun traitement.D0, Dl and D2 (application in the evening) Untreated batches receive no treatment.
3 - Sensibilisation3 - Awareness
A J3 ( le matin ), la phase de sensibilisation est mise en route par application topique de disques de papier filtre de 9 mm de diamètre sur lesquels 25 μl de composition sensibilisante ont été préalablement déposées. Quatre produits, 3 sensibilisants ( DCNB à 0,0062 %, sel de nickel à 0,1 %, fragrance mix, Stallerpatch Diagnostic Epicutane de Stallergenes S. A ) et un produit irritant ( SDS à 0,1 % ) sont utilisés.At D3 (in the morning), the sensitization phase is started by topical application of discs of filter paper 9 mm in diameter on which 25 μl of sensitizing composition have been previously deposited. Four products, 3 sensitizers (DCNB 0.0062%, nickel salt 0.1%, fragrance mix, Stallerpatch Diagnostic Epicutane from Stallergenes S. A) and an irritant product (SDS 0.1%) are used.
4 - Prélèvement pour l'histologie4 - Sampling for histology
Trois explants de chaque lot sont prélevés à J4 soit 24 heures après sensibilisation. Les explants prélevés sont coupés en deux, une moitié est fixée dans du liquide de Bouin ordinaire tandis que l'autre moitié est congelée à -80°C, en vue des différents marquages immunologiques.Three explants from each batch are taken on D4, ie 24 hours after sensitization. The explants taken are cut in half, one half is fixed in ordinary Bouin liquid while the other half is frozen at -80 ° C, for the different immunological markings.
Méthodes d'observation des cellules de Langerhans II existe plusieurs méthodes d'observation des CLMethods of observing Langerhans cells There are several methods of observing CL
La coloration au trichrome de Masson : les cellules de Langerhans apparaissent comme des cellules à cytoplasme clair dans l'épiderme ; de plus, il est difficile de les identifier dans le derme.Masson trichrome staining: Langerhans cells appear as cells with clear cytoplasm in the epidermis; moreover, it is difficult to identify them in the dermis.
- La réaction ATPasique : la réaction de l' ATP avec la membrane des CL permet de les visualiser en brun- noir, mais elle n'est pas spécifique des CL.- The ATPase reaction: the reaction of ATP with the LC membrane makes it possible to visualize them in black-brown, but it is not specific for LCs.
- Le marquage de l'antigène CDla : les CL sont CD la positif dans l'épiderme et dans le derme. Cependant, au fur et à mesure de leur migration, elles deviennent CDla négative, HLA-DR positive et CD36 positive.- Labeling of the CDla antigen: the CL are CD positive in the epidermis and in the dermis. However, as they migrate, they become CDla negative, HLA-DR positive and CD36 positive.
5- Colorations et Marquages5- Colors and Markings
Après déshydratation et imprégnation en paraffine, les explants fixés dans le Bouin sont mis en bloc, coupés et une coloration au trichrome de Masson est réalisée pour l'analyse morphologique générale.After dehydration and paraffin impregnation, the explants fixed in the Bouin are placed in a block, cut and staining with Masson trichrome is performed for the general morphological analysis.
Le marquage immunologique des cellules de Langerhans par l'anti-CDla est réalisé sur les coupes congelées coupées au cryostat.The immunological labeling of Langerhans cells with anti-CDla is carried out on frozen sections cut with a cryostat.
Les cellules de Langerhans sont assez nombreuses dans l'épiderme. Leur dendricité est diminuée. Elles sont modérément présentes dans le derme papillaire.Langerhans cells are quite numerous in the epidermis. Their dendricity is reduced. They are moderately present in the papillary dermis.
RESULTATSRESULTS
Morphologie généraleGeneral morphology
Les modifications de la structure cutanée ont été recherchées dans les différents compartiments : épiderme, jonction dermo-épidermique, derme papillaire et réticulaire supérieur.Changes in the skin structure were sought in the various compartments: epidermis, dermo-epidermal junction, papillary and upper reticular dermis.
Marquage anti- CD1 a Les cellules de Langerhans marquées sont observées dans les différentes couches de l'épiderme, au niveau de la jonction dermo- épidermique (JDE ) et dans le derme papillaire et réticulaire supérieur.Anti-CD1 marking a The marked Langerhans cells are observed in the different layers of the epidermis, at the dermo-epidermal junction (JDE) and in the papillary and upper reticular dermis.
Les observations à J4 TémoinObservations to D4 Witness
La morphologie générale est bonne et identique à celle observée pour le témoin à J0. Les cellules de Langerhans sont nombreuses, dendritiques et bien présentes dans les différents compartiments épidermiques. Elles sont, par zone, plus ou moins présentes dans le derme papillaire.The general morphology is good and identical to that observed for the control on D0. Langerhans cells are numerous, dendritic and well present in the various epidermal compartments. They are, by area, more or less present in the papillary dermis.
En présence d'une composition selon l'invention La morphologie générale est bonne et identique à celle observée pour le témoin à J0.In the presence of a composition according to the invention The general morphology is good and identical to that observed for the control on D0.
Les cellules de Langerhans sont nombreuses avec une bonne morphologie. Elles sont bien présentes dans les différents compartiments épidermiques et peu visibles dans le derme papillaire.Langerhans cells are numerous with a good morphology. They are present in the various epidermal compartments and hardly visible in the papillary dermis.
Après application du SDS à 0,1 %>After application of SDS at 0.1%>
La morphologie générale est bonne et identique à celle observée pour le témoin à J0.The general morphology is good and identical to that observed for the control on D0.
En présence d'une composition selon l'invention et du SDS à 0,1% La morphologie générale est bonne et identique à celle observée pour le témoin à J0. Les cellules de Langerhans sont nombreuses dans l'épiderme et souvent localisées dans la couche basale. Leur dendricité est bonne. Elles sont très peu présentes dans le derme papillaire.In the presence of a composition according to the invention and 0.1% SDS The general morphology is good and identical to that observed for the control on D0. Langerhans cells are numerous in the epidermis and often localized in the basal layer. Their dendricity is good. They are very little present in the papillary dermis.
Après application de nitrate de nickel à 0,1% La morphologie générale est bonne et identique à celle observée pour le témoin à J0.After application of 0.1% nickel nitrate The general morphology is good and identical to that observed for the control on D0.
Les cellules de Langerhans sont peu nombreuses dans l'épiderme et souvent localisées près de la JDE. Leur dendricité est diminuée.Langerhans cells are few in the epidermis and often located near the JDE. Their dendricity is reduced.
En présence d'une composition selon Vin vention. et de nitrate de nickel à 0,1 %: La morphologie générale est bonne et identique à celle observée pour le témoin à J0. Les cellules de Langerhans sont nombreuses dans l'épiderme, bien dendritiques et localisées dans les différents compartiments épidermiques. Elles sont peu présentes dans le derme papillaire.In the presence of a composition according to Vin vention. and 0.1% nickel nitrate: The general morphology is good and identical to that observed for the control on D0. Langerhans cells are numerous in the epidermis, well dendritic and localized in the various epidermal compartments. They are little present in the papillary dermis.
Après application deDNCBà 0,0062 %After application of DNCB at 0.0062%
La morphologie générale est bonne et identique à celle observée pour le témoin à J0.The general morphology is good and identical to that observed for the control on D0.
Les cellules de Langerhans sont peu nombreuses dans l'épiderme et leur dendricité est diminuée. Elles sont nettement visibles dans le derme papillaire.Langerhans cells are few in the epidermis and their dendricity is reduced. They are clearly visible in the papillary dermis.
En présence d'une composition selon l'invention et de DNCB à 0, 0062 % La morphologie générale est bonne et identique à celle observée pour le témoin à J0. Les cellules de Langerhans sont plus nombreuses dans l'épiderme. Certaines sont situées dans la couche basale et elles sont bien dendritiques. Elles sont modérément présentes dans le derme papillaire.In the presence of a composition according to the invention and of DNCB at 0.0062% The general morphology is good and identical to that observed for the control on D0. Langerhans cells are more numerous in the epidermis. Some are located in the basal layer and are well dendritic. They are moderately present in the papillary dermis.
CONCLUSIONCONCLUSION
Quelque soit le produit appliqué, les observations morphologiques ne montrent pas de réactions de type orthoergique.Whatever the product applied, morphological observations do not show orthoergic type reactions.
Dans ces conditions expérimentales, l'application de la composition selon l'invention induit une activité de protection des cellules de Langerhans nette avec le nitrate de nickel, modérée avec le DNCB et légère avec le SDS.Under these experimental conditions, the application of the composition according to the invention induces a clear Langerhans cell protection activity with nickel nitrate, moderate with DNCB and slight with SDS.
CONCLUSION GENERALEGENERAL CONCLUSION
Cette activité sur les cellules de Langerhans montre un effet apaisant et/ou protecteur vis à vis de substances provoquant l'allergie de contact, notamment celle provoquée par le nickel. Les figures ci-annexées représentent des coupes de tissu épidermique et dermique montrant des zones d'altération plus ou moins profondes après exposition à un solvant comme le toluène (figures 2A et 2B), à un agent tensioactif comme le SDS à 20 % , à un acide fort comme l'acide chlorhydrique et à une base forte comme l'ammoniaque à 10 % en comparaison avec les résultats obtenus, avec l'agent irritant et avec une composition selon l'invention, ainsi qu'en comparaison avec un témoin et avec la préparation selon l'invention seule.This activity on Langerhans cells shows a soothing and / or protective effect with respect to substances causing contact allergy, in particular that caused by nickel. The appended figures represent sections of epidermal and dermal tissue showing zones of more or less deep alteration after exposure to a solvent such as toluene (FIGS. 2A and 2B), to a surfactant such as 20% SDS, at a strong acid like hydrochloric acid and a strong base like 10% ammonia in comparison with the results obtained, with the irritant and with a composition according to the invention, as well as in comparison with a control and with the preparation according to the invention alone.
Ces coupes montrent clairement l'effet protecteur et restructurant des compositions selon l'invention.These sections clearly show the protective and restructuring effect of the compositions according to the invention.
Exemple VIIExample VII
Etude des effets protecteurs d'une crème barrière selon l'invention vis à vis de la pénétration cutanée du nitrate de nickelStudy of the protective effects of a barrier cream according to the invention with respect to the cutaneous penetration of nickel nitrate
L'objectif de cette étude a eu pour but d'évaluer l'activité protectrice de la crème barrière selon l'invention vis-à-vis d'un allergène très courant le nickel, sous forme de sel concentré à 5% et 10%. La visualisation de la pénétration du nitrate de nickel a été réalisée grâce à une coloration spécifiques de coupes d'expiants de peau humaine. Les résultats ont montré que sans protection, le nitrate de nickel diffusait dans le stratum corneum, d'autant plus profondément que les temps de contact sont élevés. Inversement, grâce à un pré-traitement par la crème barrière, le nitrate de nickel reste strictement localisé à la surface du stratum cormneum et ne pénètre pas, quel que soient les concentrations d'allergène et le temps d'exposition testés.The objective of this study was to assess the protective activity of the barrier cream according to the invention against a very common allergen nickel, in the form of concentrated salt at 5% and 10% . The visualization of the penetration of nickel nitrate was carried out by means of a specific coloration of sections of explants of human skin. The results showed that without protection, the nickel nitrate diffuses in the stratum corneum, all the more deeply as the contact times are high. Conversely, thanks to a pre-treatment with the barrier cream, the nickel nitrate remains strictly localized on the surface of the stratum cormneum and does not penetrate, whatever the allergen concentrations and the exposure time tested.
Ces résultats prouvent l'efficacité isolante protectrice de la crème barrière selon l'invention étudiée, vis-à-vis de la pénétration du nitrate de nickel à travers le stratum corneum.These results prove the protective insulating effectiveness of the barrier cream according to the invention studied, with respect to the penetration of nickel nitrate through the stratum corneum.
Le nickel est un allergène commun. Il constitue une des causes les plus répandues d'eczéma de contact allergique (1, 2). La fréquence de sensibilisation cutanée au nickel est en constante augmentation. Elle concerne environ 10% de la population européenne et les femmes sont majoritairement concernée (3). Les dermites de contact allergiques induites par le nickel, d'origine professionnelle (4, 5) ou domestique (6) se révèlent souvent très handicapantes dans la vie quotidienne et l'éviction de l'allergène reste un véritable problème. Ainsi , certains professionnels comme les coiffeurs (7) ou les mécaniciens (8) sont particulièrement exposés aux dermites de contact allergiques. Celles-ci peuvent également survenir au contact de vêtements (boutons des jeans, boucle de ceinture), de lunettes, de bijoux fantaisie, de matériel de cuisine ou encore de pièce de monnaie. L'ubiquité du nickel rend son éviction difficile, d'où la nécessité de protéger le tégument pour éviter les récidives. Le port de gants et souvent mal supporté, voire incompatible avec certaines activités. Les crèmes barrières représentent donc une alternative thérapeutiques prometteuse. Elles se révèlent efficaces et particulièrement bien acceptées, même dans l'exercice professionnel (9, 10).Nickel is a common allergen. It is one of the most common causes of allergic contact eczema (1, 2). The frequency of skin sensitization to nickel is constantly increasing. It concerns around 10% of the European population and women are mainly concerned (3). Nickel-induced allergic contact dermatitis of professional (4, 5) or domestic (6) origin often proves to be very disabling in everyday life and the elimination of the allergen remains a real problem. Thus, some professionals such as hairdressers (7) or mechanics (8) are particularly exposed to allergic contact dermatitis. These can also occur in contact with clothing (jeans buttons, belt buckle), glasses, costume jewelry, kitchen equipment or even coins. The ubiquity of nickel makes it crowded out difficult, hence the need to protect the seed coat to avoid recurrences. Gloves are often poorly supported, even incompatible with certain activities. Barrier creams therefore represent a promising therapeutic alternative. They appear to be effective and particularly well accepted, even in professional practice (9, 10).
Cette étude a eu pour but d'évaluer ex-vivo, l'activité protectrice d'une crème barrière, formulée autour d'un nouvel actif conformément à l'invention barrière, formulée autour d'un nouvel actif conformément à l'invention vis-à-vis de la pénétration du nitrate de nickel, testé à deux concentrations : 5 et 10%>.The purpose of this study was to evaluate ex-vivo, the protective activity of a barrier cream, formulated around a new active ingredient in accordance with the invention. Barrier, formulated around a new active ingredient in accordance with the invention. -with respect to the penetration of nickel nitrate, tested at two concentrations: 5 and 10%>.
Matériel et méthodeMaterial and method
Cette étude a été réalisée ex-vivo sur 42 explants de peau humaine, obtenus à partir d'une plastie abdominale d'un sujet caucasien âgé de 50 ans. Ces explants ont été maintenus en survie dans un milieu spécifique BEM (BIO-EC's Explants Médium), puis ont été répartis en six lots : lot témoin (T) non traité, lot traité par le nitrate de nickel à 5% (SI), lot traité par le nitrate de nickel à 10% (S2), lot traité par la crème barrière seule (BT), lot traité par la crème barrière puis le nitrate de nickel 5% (BS1), lot traité par la crème barrière et le nitrate de nickel 10% (BS2). A J0, les explants sont placés, chacun, dans 2 ml de milieu de culture. Les explants témoins (T) ne reçoivent aucun traitement. La crème barrière est appliquée sur les explants concernés à raison de 4 mg/cm2, suivi d'une période de séchage de 15 min.This study was carried out ex-vivo on 42 explants of human skin, obtained from an abdominal plasty of a Caucasian subject aged 50 years. These explants were maintained in survival in a specific BEM medium (BIO-EC's Explants Medium), then were divided into six batches: control batch (T) untreated, batch treated with 5% nickel nitrate (SI), batch treated with 10% nickel nitrate (S2), batch treated with barrier cream alone (BT), batch treated with barrier cream and then nickel nitrate 5% (BS1), batch treated with barrier cream and 10% nickel nitrate (BS2). On D0, the explants are each placed in 2 ml of culture medium. Control explants (T) receive no treatment. The barrier cream is applied to the explants concerned at a rate of 4 mg / cm 2 , followed by a drying period of 15 min.
Les deux solutions de nitrate de nickel à 5% ou 10% sont appliquées sur les lots SI, S2, BS1 et BS2 à l'aide d'un disque de papier filtre imprégné de 25μl de chaque solution. Ces disques restent en contact avec les explants pendant 24 ou 48 heures. Puis 3 explants de chaque lot sont prélevés et coupés en deux. Un demi-explant est congelé et conservé à -80°C jusqu'à la réalisation de coupes à congélation (5μm) qui sont alors colorées selon la méthode au diméthylglyoxime, identifiant spécifiquement le nickel. Les observations des coupes sont ensuite réalisées au microscope optique. La présence de nitrate de nickel se traduit par une coloration rose- violet se développant après quelques minutes de contact.The two 5% or 10% nickel nitrate solutions are applied to batches SI, S2, BS1 and BS2 using a filter paper disc impregnated with 25 μl of each solution. These discs remain in contact with the explants for 24 or 48 hours. Then 3 explants from each batch are removed and cut in half. Half an explant is frozen and stored at -80 ° C until freezing sections (5 μm) are produced, which are then stained according to the dimethylglyoxime method, specifically identifying nickel. The observations of the sections are then carried out under an optical microscope. The presence of nickel nitrate results in a pink-purple coloration developing after a few minutes of contact.
L'autre demi-explant de chaque lot est fixé dans du liquide de Bouin ordinaire, imprégnés en paraffine, mis en bloc et les coupes (5μm) sont réalisées. Ces coupes, colorées au trichrome de Masson, ont pour but d'examiner sous microscopie optique la morphologie générale et de confirmer l'absence de phénomène irritatif au sein de la structure épidermique.The other half-explant of each batch is fixed in ordinary Bouin liquid, impregnated with paraffin, placed in a block and the cuts (5 μm) are made. The purpose of these sections, colored with Masson trichrome, is to examine the general morphology under light microscopy and to confirm the absence of an irritant phenomenon within the epidermal structure.
Produit étudié La crème barrière étudiée est une émulsion eau dans huile renfermant le principe actif selon l'invention. Ce nouveau principe actif est une association de deux polymères :Product studied The barrier cream studied is a water-in-oil emulsion containing the active principle according to the invention. This new active ingredient is a combination of two polymers:
- un polymère de phosphorylcholine : de structure biomimétique, cette molécule amphiphile s'intègre dans le stratum corneum (SC) jusqu'à 10 μm de profondeur et stabilise les structures lamellaires inter-cornéocytaires. Ce polymère possède une forte capacité de rétention de l'eau dans le SC.- a phosphorylcholine polymer: of biomimetic structure, this amphiphilic molecule integrates into the stratum corneum (SC) up to 10 μm deep and stabilizes the inter-corneocytic lamellar structures. This polymer has a high capacity for retaining water in the SC.
- un polymère de pyrrolidone : c'est un actif de protection qui agit en surface en formant un réseau de mailles très serrées capable de piéger par des liaisons ioniques des agents exogènes irritants, tels que métaux lourds, colorants', solvants, détergents.- a pyrrolidone polymer: this is a protective active which acts on the surface by forming a network of meshes tight capable of trapping by ionic bonds irritants exogenous agents, such as heavy metals, dyes', solvents, detergents.
La combinaison de ces deux principes actifs complémentaires qui constituent l'élément actif de la composition selon l'invention, réalise ainsi une barrière anti-agression cutanée.The combination of these two complementary active principles which constitute the active element of the composition according to the invention, thus produces an anti-skin aggression barrier.
RésultatsResults
• Morphologie générale• General morphology
Les explants traités par la crème barrière seule selon l'invention sont histologiquement semblables aux explants témoins non traités : l'épiderme stratifié présente un SC d'épaisseur moyenne, bien feuilleté et légèrement kératinisé à la base. Ainsi l'application de la crème barrière ne modifie pas la morphologie générale de l'épiderme et confirme l'absence d'irritation du produit appliqué.The explants treated with the barrier cream alone according to the invention are histologically similar to the untreated control explants: the laminated epidermis has a thick SC medium, well flaky and slightly keratinized at the base. Thus the application of the barrier cream does not modify the general morphology of the epidermis and confirms the absence of irritation of the product applied.
«Expiants non exposés au nitrate de nickel"Explants not exposed to nickel nitrate
Aucune coloration liée à la présence du nickel n'est observée, validant ainsi la spécificité de la méthode au diméthylglyoxime.No coloration linked to the presence of nickel is observed, thus validating the specificity of the dimethylglyoxime method.
•Explants exposés au nitrate de nickel Explants exposés au nitrate de nickel 5%Explants exposed to nickel nitrate Explants exposed to nickel nitrate 5%
Explants non pré-traitésExplants not pre-treated
Après 24h de contact et en absence de crème barrière, une coloration rose-violet modérée est observée à la surface et dans l'ensemble du SC. Après 48h de contact, la coloration rose-violet reste modérée dans les couches les plus superficielles, plus intense dans les couches profondes du SC. Elle a commencé à diffuser au sein des couches épidermiques sous - jacentes. Explants pré-traités Quel que soit le temps de contact avec l'allergène, en présence de crème barrière la coloration rose reste toujours bien localisée à la surface du SC. La coloration n'est pas observée dans les couches profondes du SC.After 24 hours of contact and in the absence of barrier cream, a moderate pink-violet coloration is observed on the surface and throughout the SC. After 48 hours of contact, the pink-purple coloration remains moderate in the most superficial layers, more intense in the deep layers of the SC. It began to diffuse within the underlying epidermal layers. Explants pre-treated Whatever the contact time with the allergen, in the presence of barrier cream, the pink coloration always remains well localized on the surface of the SC. Staining is not observed in the deep layers of the SC.
Explants exposés au nitrate de nickel 10%Explants exposed to 10% nickel nitrate
Explants non pré-traités Après 24h de contact, en absence de crème barrière selon l'invention, une coloration rose- violet est observée dans l'ensemble du SC, avec une diffusion dans les couches épidermiques sous - jacentes après 48h de contact. Explants pré-traitésExplants not pretreated After 24 hours of contact, in the absence of the barrier cream according to the invention, a pink-purple coloration is observed throughout the SC, with diffusion into the underlying epidermal layers after 48 hours of contact. Pre-processed explants
En présence de crème barrière selon l'invention, la coloration rose, légère à 24h puis nette à 48h, se limite strictement à la surface du SC et ne diffuse pas.In the presence of barrier cream according to the invention, the pink coloration, light at 24 hours then clear at 48 hours, is strictly limited to the surface of the SC and does not diffuse.
La sensibilisation au nickel est un phénomène fréquent et c'est la forme sulfate qui est principalement mise en cause. Aussi, elle est utilisée dans les tests épicutanés en dermato- allergologie pour confirmer le diagnostic d'eczéma de contact au nickel (11). Cependant, des études récentes (12, 13) menées in vivo ont montré que des sels de nickel de nature différente diffusent dans le SC, en empruntant simultanément différentes voies de diffusion (espaces intercellulaires, cellules cornées et annexes cutanées) offrant ainsi la capacité d'induire des réactions allergiques.Sensitization to nickel is a frequent phenomenon and it is the sulphate form which is mainly called into question. Also, it is used in skin patch tests in dermatology and allergology to confirm the diagnosis of nickel contact eczema (11). However, recent studies (12, 13) carried out in vivo have shown that nickel salts of a different nature diffuse in the SC, by simultaneously using different diffusion routes (intercellular spaces, horny cells and cutaneous appendages), thus providing the ability to induce allergic reactions.
Le gradient de concentration du nickel adsorbé au niveau épidermique varie selon la nature du sel, le site anatomique, la dose et le temps d'exposition. Ainsi, sous forme nitrate, le nickel pénètre au-delà du SC, comparativement à d'autres sels : chlorure, sulfate ou acétate de nickel (14).The concentration gradient of the nickel adsorbed at the epidermal level varies according to the nature of the salt, the anatomical site, the dose and the exposure time. Thus, in the nitrate form, nickel penetrates beyond the SC, compared to other salts: chloride, sulfate or nickel acetate (14).
Dans le cadre de cette étude, les résultats confirment la capacité de diffusion du nitrate de nickel dans le SC : l'allergène pénètre facilement tout en respectant la morphologie et la structure des couches épidermiques. Indépendamment de la concentration employée, le nitrate de nickel est détectable au-delà du SC après 48h de contact. Inversement, sur peau pré-traitée par la crème barrière selon l'invention, le nitrate de nickel reste strictement localisé en surface du SC, quels que soient les concentrations et les temps de contact considérés, et les explants sont isolés et protégés de l'agent allergène.In the context of this study, the results confirm the diffusion capacity of nickel nitrate in the SC: the allergen penetrates easily while respecting the morphology and structure of the epidermal layers. Regardless of the concentration used, nickel nitrate is detectable beyond the SC after 48 hours of contact. Conversely, on skin pretreated with the barrier cream according to the invention, the nickel nitrate remains strictly localized on the surface of the SC, whatever the concentrations and the contact times considered, and the explants are isolated and protected from the allergenic agent.
Cette étude fait suite à une première expérience menée sur explants de peau humaine avec la crème barrière selon l'invention où était étudié, après marquage immunologique, le comportement des cellules de Langerhans vis à vis de deux allergènes de contact : le dinitrochlorobenzène et le nitrate de nickel. L'expérience menée avait permis de démontrer qu'en présence de crème barrière, les cellules de Langerhans restaient localisées dans le compartiment épidermique sans migration dermique, isolées des haptènes.This study follows a first experiment carried out on human skin explants with the barrier cream according to the invention in which was studied, after immunological labeling, the behavior of Langerhans cells with respect to two contact allergens: dinitrochlorobenzene and nickel nitrate. The experience led to demonstrate that in the presence of barrier cream, Langerhans cells remained localized in the epidermal compartment without dermal migration, isolated from the haptens.
La présente étude confirme les résultats de protection déjà obtenus à l'exemple IV et prouve qu'il est possible d'isoler le tégument vis à vis de la pénétration d'une substance sensibilisante grâce à l'application d'une crème barrière spécifique.The present study confirms the protection results already obtained in Example IV and proves that it is possible to isolate the seed coat from the penetration of a sensitizing substance by applying a specific barrier cream.
Ces expériences menées en laboratoire permettent d'affirmer in vitro un effet protecteur isolant de la crème barrière selon l'invention qui présente d'ores et déjà des perspectives prometteuses dans la prise en charge thérapeutique de patients souffrant de dermatoses de contact allergiques, quelles soient ou non professionnelles.These laboratory experiments make it possible to confirm in vitro an insulating protective effect of the barrier cream according to the invention which already has promising prospects in the therapeutic management of patients suffering from allergic contact dermatoses, whatever or unprofessional.
RéférencesReferences
1 - Sertoli A., Francalanci S., Acciai M.C., Gola M. Epidemiological survey of contact dermatitis in Italy (1984-1993) by GIRDCA (Gruppo Italiano Ricerca Dermatiti da Contatto e Ambientali). Am. J. Contact. Dermat. 1999 ; 10 (1) : 18-30.1 - Sertoli A., Francalanci S., Acciai M.C., Gola M. Epidemiological survey of contact dermatitis in Italy (1984-1993) by GIRDCA (Gruppo Italiano Ricerca Dermatiti da Contatto e Ambientali). Am. J. Contact. Dermat. 1999; 10 (1): 18-30.
2 - Kucenic M.J., Belsito D.N. Occupational allergie contact dermatitis is more prévalent than irritant contact dermatitis : A 5-year study. J. Am. Acad. Dermatol. 2002 ; 46 (5) : 695-699.2 - Kucenic M.J., Belsito D.N. Occupational allergy contact dermatitis is more prevalent than irritant contact dermatitis: A 5-year study. J. Am. Acad. Dermatol. 2002; 46 (5): 695-699.
3 - Uter W., Pfahlberg A., Gefeller O., Geier J., Schnuch A. Risk factors for contact allergy to nickel - results of a multifactorial analysis. Contact Dermatitis 2003 ; 48 (1) : 33-38. 4 - Shah M., Lewis F.M., Gawkrodger D.J. Nickel as an occupational allergen. A survey of 368 nickel-sensitive subjects. Arch. Dermatol. 1998 Oct ; 134 (10) : 1231-1236.3 - Uter W., Pfahlberg A., Gefeller O., Geier J., Schnuch A. Risk factors for contact allergy to nickel - results of a multifactorial analysis. Contact Dermatitis 2003; 48 (1): 33-38. 4 - Shah M., Lewis F.M., Gawkrodger D.J. Nickel as an occupational allergen. A survey of 368 nickel-sensitive subjects. Arch. Dermatol. 1998 Oct; 134 (10): 1231-1236.
5 - Liden C. Occupational contact dermatitis due to nickel allergy. Sci. Total Environ. 1994 ; 148 (2-3) : 283-285.5 - Liden C. Occupational contact dermatitis due to nickel allergy. Sci. Total Approx. 1994; 148 (2-3): 283-285.
6 - Schollhammer M., Guillet M.H., Guillet G. Nickel et peau. Ann. Dermatol. Venereol. 1994 ; 121 : 338-345.6 - Schollhammer M., Guillet M.H., Guillet G. Nickel and skin. Ann. Dermatol. Venereol. 1994; 121: 338-345.
7 - Iorizzo M., Parente G., Nincenzi C, Pazzaglia M., Tosti A. Allergie contact dermatitis in hairdressers : frequency and source of sensitisation. Eur. J. Dermatol 2002 ; 12 : 179-182. 8 - Meding B., Barregard L., Marcus K. Hand eczéma in car mechanics. Contact Dermatitis 1994 ; 30 (3) : 129-134.7 - Iorizzo M., Parente G., Nincenzi C, Pazzaglia M., Tosti A. Allergy contact dermatitis in hairdressers: frequency and source of sensitization. Eur. J. Dermatol 2002; 12: 179-182. 8 - Meding B., Barregard L., Marcus K. Hand eczema in car mechanics. Contact Dermatitis 1994; 30 (3): 129-134.
9 - Bauer A., Kelterer D., Bartsch R., Pearson J., Stadeler M., Kleesz P., Elsner P., Williams H. Skin protection in bakers' apprentices. Contact Dermatitis 2002 ; 46 (2) : 81 -85. 10 - Perrenoud D., Gallezot D., van Melle G. The efficacy of a protective cream in a real- world apprentice hairdresser environment. Contact Dermatitis 2001 ; 45 (3) : 134-138. 11 - Bruynzeel D.P., Andersen K.E., Camasara J.G., Lachapelle J.M., Menne T., Wliite I.R. The European standard séries. European Environmental and Contact Dermatitis Research Group (EECDRG). Contact Dermatitis 1995 ; 33 (3) : 145-148. 12 - Hostynek J.J.., Dreher F., Pelosi A., Anigbogu A.,. Maibach H.I. Human stratum comeum pénétration by nickel. In vivo study of depth distribution after occlusive application of the métal as powder. Acta. Derm. Venereol. Suppl (Stockh). 2001 ; 212 : 5-10.9 - Bauer A., Kelterer D., Bartsch R., Pearson J., Stadeler M., Kleesz P., Elsner P., Williams H. Skin protection in bakers' apprentices. Contact Dermatitis 2002; 46 (2): 81 -85. 10 - Perrenoud D., Gallezot D., van Melle G. The efficacy of a protective cream in a real-world apprentice hairdresser environment. Contact Dermatitis 2001; 45 (3): 134-138. 11 - Bruynzeel DP, Andersen KE, Camasara JG, Lachapelle JM, Menne T., Wliite IR The European standard series. European Environmental and Contact Dermatitis Research Group (EECDRG). Contact Dermatitis 1995; 33 (3): 145-148. 12 - Hostynek JJ., Dreher F., Pelosi A., Anigbogu A . , . Maibach HI Human stratum comeum penetration by nickel. In vivo study of depth distribution after occlusive application of the metal as powder. Acta. Derm. Venereol. Suppl (Stockh). 2001; 212: 5-10.
13 - Tanojo H., Hostynek J.J., Mountford H.S., Maibach H.I. In vitro permeation of nickel salts through human stratum corneum. Acta. Derm. Venereol. Suppl. (Stockh) 2001 ; 212 : 19-23.13 - Tanojo H., Hostynek J.J., Mountford H.S., Maibach H.I. In vitro permeation of nickel salts through human stratum corneum. Acta. Derm. Venereol. Suppl. (Stockh) 2001; 212: 19-23.
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Claims

REVENDICATIONS
1- Nouvelles compositions dermatologiques et/ou cosmétiques caractérisées en ce qu'elles contiennent comme principes actifs un homopolymère de N-vinyl 2-pyrrolidone et un copolymère de 2-méthacryloyloxylphosphorylcholine et de méthacrylate de n-butyle associés ou en mélange avec un ou plusieurs excipients, ou véhicules inertes, non toxiques, dermatologiquement acceptables.1- New dermatological and / or cosmetic compositions characterized in that they contain as active principles a homopolymer of N-vinyl 2-pyrrolidone and a copolymer of 2-methacryloyloxylphosphorylcholine and n-butyl methacrylate associated or in mixture with one or more excipients, or inert, non-toxic, dermatologically acceptable vehicles.
2- Nouvelles compositions dermatologiques et/ou cosmétiques selon la revendication 1, dans lesquelles l'homopolymère de N-vinyl 2-pyrrolidone utilisé est celui commercialisé sous les marques Plasdone K-25, Plasdone K-26/28, Plasdone K-29/32 ou Plasdone K-90.2- New dermatological and / or cosmetic compositions according to claim 1, in which the N-vinyl 2-pyrrolidone homopolymer used is that marketed under the brands Plasdone K-25, Plasdone K-26/28, Plasdone K-29 / 32 or Plasdone K-90.
3- Nouvelles compositions dermatologiques et/ou cosmétiques selon la revendication 1, dans lesquelles l'homopolymère de N-vinyl 2-pyrrolidone est celui commercialisé sous la dénomination POVIDERM SK3.3- New dermatological and / or cosmetic compositions according to claim 1, in which the homopolymer of N-vinyl 2-pyrrolidone is that marketed under the name POVIDERM SK3.
4- Nouvelles compositions dermatologiques et/ou cosmétiques selon la revendication 1, dans lesquelles le copolymère de 2-méthylacrylate de n-butyle et de 2-métacrylate éthylphosphorylcholine a la formule suivante I :4- New dermatological and / or cosmetic compositions according to claim 1, in which the copolymer of n-butyl 2-methylacrylate and of ethylphosphorylcholine 2-metacrylate has the following formula I:
X 5- Nouvelles compositions dermatologiques et/ou cosmétiques selon la revendication 1, dans lesquelles la teneur en polyvinylpyrrolidone varie de 0,1 à 4 %. X 5- New dermatological and / or cosmetic compositions according to claim 1, in which the polyvinylpyrrolidone content varies from 0.1 to 4%.
6- Nouvelles compositions dermatologiques et/ou cosmétiques selon la revendication 1, dans lesquelles le teneur en polyvinylpyrrolidone s'échelonne de 1,5 à 2,5 %.6- New dermatological and / or cosmetic compositions according to claim 1, in which the polyvinylpyrrolidone content ranges from 1.5 to 2.5%.
7- Nouvelles compositions dermatologiques et/ou cosmétiques selon la revendication 1, dans lesquelles la teneur en PMPC s'échelonne de 0,1 à 4 % par rapport à la composition totale.7. New dermatological and / or cosmetic compositions according to claim 1, in which the PMPC content ranges from 0.1 to 4% relative to the total composition.
8- Nouvelles compositions dermatologiques et/ou cosmétiques selon la revendication 1, dans lesquelles la teneur en PMPC s'échelonne entre 1,8 et 2,5 % par rapport à la composition totale.8- New dermatological and / or cosmetic compositions according to claim 1, in which the PMPC content ranges between 1.8 and 2.5% relative to the total composition.
9- Nouvelles compositions dermatologiques et/ou cosmétiques selon la revendication 1, qui renferment en outre des silicones.9- New dermatological and / or cosmetic compositions according to claim 1, which also contain silicones.
10- Nouvelles compositions dermatologiques et/ou cosmétiques selon la revendication 1, qui renferment en outre au moins un agent épaississant, un agent diluant, un agent de pénétration, un agent aromatisant et/ou un agent conservateur.10- New dermatological and / or cosmetic compositions according to claim 1, which additionally contain at least one thickening agent, a diluting agent, a penetration agent, a flavoring agent and / or a preservative.
11- Procédé de préparation des compositions dermatologiques et/ou cosmétiques selon l'une au moins des revendications précédentes caractérisées en ce qu'on mélange, broie ou fond les principes actifs et en ce qu'on les incorpore à un excipient ou à un véhicule puis aromatise la préparation et on la répartie dans des emballages ou des flaconnages de forme et de volume appropriés.11- Process for the preparation of dermatological and / or cosmetic compositions according to at least one of the preceding claims, characterized in that the active principles are mixed, ground or melted and in that they are incorporated into an excipient or a vehicle then flavor the preparation and distribute it in packaging or bottles of suitable shape and volume.
12- Nouvelles compositions dermatologiques et/ou cosmétiques selon l'une des revendications 1 à 10, présentées sous forme de crèmes, de pommades, de gels anhydres ou aqueux, de lotions, d'émulsions H/E ou E/H, de pains, de savons, de laits pour la douche ou similaires. 12- New dermatological and / or cosmetic compositions according to one of claims 1 to 10, presented in the form of creams, ointments, anhydrous or aqueous gels, lotions, O / W or W / O emulsions, breads , soaps, shower milks or the like.
EP03767863A 2002-10-31 2003-10-29 Novel dermatological and/or cosmetologic hydrating and anti-irritation compositions Withdrawn EP1641433A1 (en)

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FR0213663A FR2846555B1 (en) 2002-10-31 2002-10-31 NOVEL MOISTURIZING AND ANTI-IRRITATING DERMATOLOGICAL AND / OR COSMETOLOGICAL COMPOSITIONS
PCT/FR2003/003232 WO2004041235A1 (en) 2002-10-31 2003-10-29 Novel dermatological and/or cosmetologic hydrating and anti-irritation compositions

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EP1641433A1 true EP1641433A1 (en) 2006-04-05

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EP03767863A Withdrawn EP1641433A1 (en) 2002-10-31 2003-10-29 Novel dermatological and/or cosmetologic hydrating and anti-irritation compositions

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EP (1) EP1641433A1 (en)
AU (1) AU2003292297A1 (en)
FR (1) FR2846555B1 (en)
WO (1) WO2004041235A1 (en)

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FR2884142A1 (en) * 2005-04-06 2006-10-13 Oreal Cosmetic composition for use as makeup and/or care composition for lips and/or skin, e.g. lipstick or foundation, contains polymer comprising graft or block of polyolefinic nature or polymeric unit derived from alpha-olefin
US8071667B2 (en) * 2005-06-02 2011-12-06 Nalco Company Compositions comprising (poly) alpha olefins
FR2890558B1 (en) * 2005-09-15 2007-10-12 Oreal MICROCAPSULES WITH AQUEOUS HEART AND THEIR USE IN COSMETICS
FR2895247B1 (en) * 2005-12-26 2008-06-06 Dermatologiques D Uriage Sa La COMPOSITIONS BASED ON A DERMATOLOGICAL AND COSMETIC COMPLEX AND THEIR USES FOR LIMITING SENSITIZATION
PT1815844E (en) * 2005-12-26 2015-07-02 Dermatologiques D Uriage Lab Photoprotecting compositions with reduced risk of skin sensitisation
FR2910287B1 (en) * 2006-12-20 2009-04-17 Oreal COSMETIC PRODUCT COMPRISING SILICONE COMPOUNDS AND A MOISTURIZING POLYMER
FR2929847B1 (en) * 2008-04-11 2013-03-29 Dermatologique Uriage Lab DERMATOLOGICAL AND / OR COSMETIC COMPOSITION PROTECTING THE SKIN AND MUCOUS MEMBRANES
FR2936150B1 (en) * 2008-09-19 2013-09-06 Dermathologiques D Uriage Lab NEW DERMATOLOGICAL COMPOSITIONS PROTECTING THE SKIN AND MUCOUS MEMBRANES
FR2929846B1 (en) * 2008-04-11 2019-12-27 Laboratoires Dermatologiques D'uriage SKIN PROTECTIVE DERMATOLOGICAL AND / OR COSMETIC COMPOSITION
JP6742312B2 (en) * 2014-08-05 2020-08-19 アマンタン・エクスペール Skin protection composition

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JP2000178123A (en) * 1998-12-15 2000-06-27 Nof Corp Cosmetic substrate composition and cosmetic
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Non-Patent Citations (1)

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See references of WO2004041235A1 *

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WO2004041235A1 (en) 2004-05-21
FR2846555A1 (en) 2004-05-07
FR2846555B1 (en) 2006-08-11
AU2003292297A1 (en) 2004-06-07

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