FR2860718A1 - NOVEL FORMULATION AND ITS APPLICATIONS IN THE COSMETIC OR PHARMACEUTICAL FIELDS - Google Patents

Abstract

The present invention relates to the field of the necessities of life and more particularly to the fields of cosmetology, pharmacy and more specifically dermatology. The present invention more particularly relates to new aqueous formulations comprising, as active ingredient at least cromoglicic acid and / or one of its salts and / or esters, combined with a gelling agent optionally combined with a suitable pH agent. The present invention also relates to the use of this combination for the production of cosmetic, pharmaceutical and especially dermatological compositions intended to prevent and / or treat the uncomfortable, unsightly and / or painful manifestations of the skin and / or mucous membranes. The present invention also relates to a cosmetic care method for sensitive skin, intolerant, hypersensitive or atopic.Ces compositions relate in particular to the realization of care, treatments, sun care, makeup of intolerant skin of humans or the animal.

Description

NEW FORMULATION AND ITS APPLICATIONS IN COSMETIC DOMAINS OR

PHARMACEUTICAL

  The present invention relates to the field of the necessities of life and more particularly to the fields of cosmetology, pharmacy and more specifically dermatology.

  The present invention relates to novel formulations based on cromoglicic acid. It relates more particularly to new aqueous formulations comprising, as active principle, at least cromoglicic acid and / or a salt thereof and / or esters, combined with a gelling agent optionally combined with a suitable pH agent. . The present invention also relates to the use of this combination for the production of cosmetic or pharmaceutical compositions, especially dermatological compositions, for preventing and / or reducing cutaneous, nasal, ocular and / or digestive, uncomfortable, unsightly or painful manifestations of the skin, mucous membranes and / or integuments, especially sensitive, hypersensitive, intolerant or atopic. These compositions, although they can be used orally, are more specifically intended for topical application and in particular for the skin. The present invention also relates to the use of this combination for the production of hypoallergenic cosmetic or pharmaceutical compositions. The present invention also relates to a cosmetic care method for sensitive, hypersensitive, intolerant or atopic skin.

  Skin sensitivity is a phenomenon that has been increasing steadily for nearly a century and more over the past decade. Qualified as a sign of modern times, of a phenomenon of society, it would be linked in particular to industrialization. The skin is, in fact, constantly exposed to the irritating agents that surround us. It is common then that it develops an increased sensitivity to these daily aggressions and, aggression continues, it shows an altered, excessive response to substances previously well tolerated: it is the allergic state. Skin sensitivity is thus often a first step towards skin allergy.

  Skin sensitivity can be expressed by various skin manifestations such as redness, dry skin, cracks, flaking, itching, tightness, irritation, swelling, many intolerance reactions that can lead to real diseases inflammatory diseases among which are atopic diseases. The most common are contact dermatitis and atopic dermatitis, also known as eczema, urticaria and especially contact urticaria, common urticaria and solar urticaria.

  Whether due to a natural or acquired sensitivity, specific or not, the root causes of all these cutaneous manifestations are still uncertain. Some exogenous factors that may trigger, reveal or aggravate such skin reactions have been identified. Thus, polluting particles of the environment, dust, pollen, chemicals of hygiene products, tobacco, metal alloys, climatic variations are irritating agents for the skin. Cosmetics or dermatological products, because of excipients, solvents, dyes, perfumes or sometimes irritating active ingredients that they contain, are also part of these potentially sensitizing products.

  Fragile skin, often damaged, especially atopic skins, requires daily care, including moisturizing and soothing care, to reduce discomfort, unsightliness and / or pain caused by sensitivity reactions. dermal or skin allergies. It is therefore essential that such care is specifically adapted to their reactive and intolerant nature. Studies have also shown that skins with atopic tendency provide a weaker protection than the so-called normal skins vis-a-vis the external agents, from where the necessity to fight against this fragility in order to prevent secondary infections.

  One solution is to moisturize the skin daily. However, this care is not enough, especially to avoid irritative dermatitis. Topical steroids are then widely used in skin reactions to reduce inflammation and relieve itching. However, used in the long term, this treatment has the side effect of thinning and drying the skin, which further accentuates its fragility.

  Cromoglicic acid is a known anti-inflammatory agent used locally, useful for reducing or preventing allergic-type manifestations. This compound also called cromolyn is also defined according to the nomenclature such as 1,3-di (2-carboxy-4-oxochromen-5-yloxy) -2-hydroxypropane. Its anti-allergic and anti-inflammatory local properties are due to its ability to prevent the release of chemical mediators, including histamine, responsible for anaphylactic reactions, by stabilization of the mast cell membrane.

  Thus, this active ingredient is widely used in ophthalmology as anti-allergic, in the form of 2% eye drops, sold in particular under the names Opticron (Cooper), Allergocomod (Ursapharm), Cromabak (Thea), Cromedil (Europhta).

  It is also used by the respiratory route, in the treatment of allergic asthma and allergic rhinitis, in the form of sprays, inhalers and nebulization solutions, marketed in particular under the names Lomusol and Lomudal (Aventis).

  It is almost devoid of toxicity and is also used in oral solution for the treatment of digestive and extradigestive manifestations of food allergies, and marketed in particular under the name of Nalcron (Aventis), Intercron Ge (Laphal).

  Cromoglicic acid is a compound of hydrophilic nature, soluble in water but very polar. It has the disadvantage of having a low skin penetration capacity and therefore limited effectiveness. Many excipients are then used in the topical compositions in order to obtain an effective treatment on the area of the body to be treated. Formulated with certain excipients, cromoglicic acid and its salts is recognized for its anti-allergic and anti-inflammatory properties in bronchial, conjunctival and digestive mucosal applications. However, at the cutaneous level, the usual excipients are considered insufficient. The effectiveness of cromoglicate and compositions containing it is thus very controversial at the cutaneous level. Some publications conclude that dermal cromoglicate is effective (Thirumoorthy T., Greaves, Disodium cromoglycate in atopic eczema, (1978) British Medicine Journal II: 500-501, Zachariar et al., 1979). Others showed disappointing, discontinuous results (Topical Sodium Cromoglicate in Atopic Dermatitis, Allergy, (1986) 41, 423-428) or even negative (Sondergaard J. et al., Chromones in atopic dermatitis, Arch Dermatol Res. (1980) 267 (3): 223-8). The effective concentration of the active ingredient has been the subject of numerous and very controversial studies (MG Pike et al., Failure of a new topical sodium cromoglycate formulation to improve atopic dermatitis, European Journal of Pediatrics (1988) 148: 170-178). . Vehicle type was quickly considered to be a determining factor in the efficacy of cromoglicate, which may account for these variations in efficacy (Croner, S. et al., Sodium cromoglycate in atopic eczema during childhood, Opuscula Med (1982) 26, 49-50). For many years, a lot of research has been undertaken to improve the effectiveness of cromoglicate in cutaneous application.

  Thus, the French patent application FR2517543 describes the cutaneous application of a mixture of sodium cromoglicate, dry particles of hydrophilic macromolecular material, insoluble in water and capable of swelling in contact with an aqueous fluid. The weight ratio of sodium cromoglicate to dry particles is 1: 0.05. These particles consisting for example of dextran, starch or hydroxyethyl cellulose have the function of absorbing certain constituents of low molecular weight of the blood plasma. They are then removed from the skin surface of the skin. Thus, these compositions, intended to be applied to a cutaneous wound, are either in dry form especially for the production of dressings, or in non-aqueous solution in a solvent such as PEG.

  Several tests have been reported in the literature aimed specifically at improving the passage of cromoglicate through the cutaneous wall. Thus, patent document EP0084898 discloses the use of an amount of 0.01 to 50 mg / ml of sodium cromoglicate, partially in liposome-encapsulated form, the remainder being in free form in aqueous solution. The composition thus formed can be used to treat atopic disease type skin diseases. Nevertheless, this solution makes the synthesis process of the compositions more complex, introduces formulation constraints, and increases the cost of production of the compositions. In addition, liposomes are not very stable structures and, after a long period of storage, often return to the emulsified form. Similarly, another attempt described in WO87 / 03197 has been made with microspheres formed of substances having ion exchange properties such as diethanolamine dextran. However, the use of microspheres has the same disadvantages as those mentioned above with liposomes. In addition, it is particularly difficult to control the size of these particles.

  Another patent EP0153 003 describes the use of sodium cromoglicate in micronized form and dispersed in an oily, non-aqueous vehicle for producing an oil-in-water emulsion for treating the immune reactions of the nasal and ocular mucosa. . However, this composition contains from 0.5 to 20% by weight of cromoglicate, a minimum amount of water and on the other hand a significant amount of structured oil, preferably polyethylene. This constraint then limits the shape and consistency of the composition as well as the addition of other constituents according to the compatibilities. Moreover, it has the disadvantage of being fat, which is not always pleasant to the touch. This emulsion also forms a relatively occlusive screen on the skin and may prevent it from breathing and render it comedogenic.

  In view of this technical problem of formulation, the document WO 99/60997 describes an emulsion composition containing sodium cromoglicate with an amphoteric surfactant and a cetyl alkoxy alcohol. This alcohol-surfactant combination makes it possible to neutralize the anionic and polar power of the cromoglicate. However, this composition no longer allows the addition of polar molecule. The alcohol it contains does not allow, moreover, its use on the most fragile skins. In addition, the amphoteric surfactant used consists of a set of substances some of which are potentially irritating and allergenic, such as in particular formaldehyde, or comedogenic such as sodium lauryl sulphate. Thus, such a composition is not an appropriate solution to the care of intolerant skin.

  Research has also been conducted on compounds derived from cromoglicic acid. Thus, US Pat. No. 6,262,108 B1 describes the use of a cromoglicate ester, especially of diethyl acetoacetylcromoglicate, obtained by esterification between 3oxobutanoic acid and the hydroxyl function of propanol forming diethyl cromoglicate. This type of ester is also intended to treat cutaneous allergies and has the advantage of treating rheumatoid arthritis without any side effects. Such a compound seems, by its structure, more stable and easier to administer. It is only administered parenterally or orally. It is mentioned, without any more precision as to the doses used, that this ester compound can be formulated with a large number of constituents among which hydroxypropylcellulose as binding agent. None of the experiments have been described with this component.

  The efficacy of a 1% nebulized solution of sodium cromoglicate has also been studied by Kimata et al. (Topical cromolyn solution in the treatment of young children with atopic dermatitis, Clinical and Experimental Allergy (1990), Vol 20, p281-283) As this pointed out in more recent documents, for example the patent document WO 99/60997 and In a scientific book reviewing atopic diseases (Heath Technology Assessment 2000, Vol 4, No. 37, p 46-51), numerous attempts have been made to formulate cromoglicic acid in a form applicable to the skin.

  Some researchers have even recommended in scientific publications the abandonment of cromoglicate testing to focus on finding new substances that are more effective or more easily used (Atopic Dermatitis and Cromolyn, Clin Exp Allergy (1990) 20: 243). 244). This is also the conclusion of N.-I. M Kjellman et al. , following a study on the effectiveness of an oil-in-water solution with 4% sodium cromoglicate (Topical Sodium Cromoglicate in Atopic Dermatitis, Allergy, 1986, 41, 423-428).

  It is indeed clear that none of the solutions disclosed in the prior art can solve simply, effectively and satisfactorily the problem of the cutaneous application of cromoglicic acid. These failures have thus slowed down the use of cromoglicic acid in the cosmetic, pharmaceutical and especially dermatological fields, in favor of other more effective dermal components such as conventional antihistamines or topical corticosteroids.

  Thus, there was a growing need for care and cosmetic and / or dermatological products specifically adapted for sensitive, hypersensitive, intolerant or atopic skin. This care had to respond to two contradictory prejudices: a good efficacy implying the use of specific excipient and a good topical tolerance.

  The Applicant has solved this double problem in a particularly simple and surprising way. Conducting active research on cromoglicic acid and its salts, she found that it was possible, by combining, in an aqueous solution, the cromoglicic acid with a selected gelling agent and optionally an agent of appropriate pH, from to improve the diffusion and to give it a real effectiveness in topical application and in particular cutaneous.

  Unlike the prior art, such a composition is remarkable in that the constituents it contains are sufficient to provide a soothing, calming and preventive effect of discomfort and / or unsightliness and / or manifestations painful reactions related to sensitivity or allergy reactions, cutaneous and / or mucosal. This gel can be used on all skin, even the most intolerant. Its use is also possible on the mucous membranes with good efficiency. Other excipients, if they may be present, are not essential to the effectiveness of the gelled composition according to the invention.

  The present invention thus relates to a cosmetic or pharmaceutical and in particular dermatological composition, characterized in that it contains at least cromoglicic acid and / or one of its salts and / or esters and a gelling agent selected from the group formed of a hydroxyalkylcellulose, an acrylic acid polymer and mixtures thereof, and optionally an agent of suitable pH, in an aqueous vehicle.

  The term "cromoglicic acid" and / or one of its salts and / or one of its esters is understood to mean, according to the invention, cromolyn or cromoglicic acid, cromoglicate salts and cromoglicic acid derivatives obtained by esterification of its carboxylic functions . Among the cromoglicate salts, there may be mentioned alkali or alkaline earth cromoglicates such as sodium cromoglicate, disodium cromoglicate, magnesium cromoglicate, zinc cromoglicate, aluminum cromoglicate. Preferably, according to the invention, use will be made of sodium cromoglicate and disodium cromoglicate. It will also be possible to use cromoglicic acid salts with organic bases such as a salt of diethanolamine or monoethanolamine.

  In the composition according to the invention, the gelling agent is chosen from cellulose derivatives and polymers of acrylic acid and / or their mixtures. As a cellulose derivative, it is possible to use methylcellulose, ethylcellulose, 13-hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose. In a preferred embodiment, hydroxyethylcellulose will be used. It is also possible to use a polymer of acrylic acid. The combination of this type of agents with cromoglicic acid has the additional advantage of preventing irritation that they may generate during topical application. This type of carbomer also gives good spreading properties.

  In particular, by way of non-limiting example, mention may be made of the hydroxyethylcellulose sold under the name Natrosol 250HX Pharm by the company Hercules Incorporated and the acrylic acid polymer marketed under the name Carbopol 980 NF by the company BF Goodrich and the composed of equivalent qualities.

  By creating a crosslinked network, the gelling agent increases the contact time of the cromoglicic acid and / or its salts with the application zone and improves skin penetration. This interaction between the two constituents of cromoglicic acid and the gelling agent gives the compositions according to the invention real and sufficient antiallergic properties for good effectiveness. The use of gelling agent involves, in accordance with practice, the use of pH agents necessary for the formation of this network. These pH agents are known and depend on the type of gelling agent used. By way of example, there may be mentioned ethylethanolamines and in particular triethanolamine and methyl benzyl amine.

  In general, it will be ensured that the pH of the composition is between about 4 and 8.

  The compositions according to the invention are intended for local use by oral application or by topical application and in particular cutaneous application.

  By oral application is meant, according to the invention, the oral administration for use on the digestive mucosa.

  By topical application is meant according to the invention the cutaneous application as well as the application to mucous membranes including ocular and nasal. The application, although possible in a topical manner, will be preferentially in a cutaneous manner.

  By cutaneous application is meant, according to the invention, the application to the skin of the human or animal body, including the face, the neck, the scalp, on areas of more fragile skin such as eyelids, the contour eyes, lips, the contour of the mouth, areas of skin folds including knees and elbows, areas of skin particularly exposed to physical or chemical attack such as the skin of the feet, hands.

  The compositions according to the invention are intended to be applied in humans and / or animals.

  According to a first embodiment, the composition according to the invention may be in the form of a hydrogel, consisting solely of the combination in aqueous solution of cromoglicic acid and / or one of its salts and / or esters, of the agent hydroxyalkylcellulose gelling agent, in particular hydroxyethylcellulose, and / or acrylic acid polymer optionally combined with a suitable pH agent. In this case, the composition may contain an amount of 0.1 to 20% and preferably 1 to 5% by weight of cromoglicic acid and / or a salt and / or an ester thereof, an amount of 0.1 to 10% by weight of gelling agent.

  Preferably, 0.5 to 5% hydroxyethylcellulose or 0.5 to 2% acrylic acid polymer will be used. While respecting these predefined percentages of concentrations of each constituent, the ratio of the weight concentrations between the cromoglicic acid and the gelling agent will preferably be between 2: 1 and 0.5: 1. According to a particularly simple and interesting mode, this ratio will be close to 1: 1. In these compositions, care should be taken to maintain a sufficient amount of water to allow good dispersion of the constituents and avoid excessively high gel viscosity that could result.

  For particularly fragile skin, preferentially use purified mineral water to moisturize the skin without irritating it.

  In addition, this composition is particularly remarkable in that it has a perfect stability of 5 to 50 C.

  According to a variant of the invention, such compositions may also contain the pharmaceutically and / or cosmetically acceptable vehicles or diluents, which are usual, and suitable especially as diluent, dispersing agent, other gelling agent, solid emollient, gums, resins, sunscreen agents, solvents, fillers such as modified and polymerized starches, titanium dioxide or metal stearate, pigments, preservatives, essential oils, antioxidants, pearlescent agents, dyes, perfumes, odor absorbers, pH-regulating agents or neutralizing agents, thickening agents, absorption promoters such as propylene glycol and / or urea.

  The choice and / or the quantity of the ingredients complementary to the composition will also be determined by the tolerance, the sensitivity, the specific needs of the skin on which the composition will be applied as well as by the properties and the desired consistency for the composition according to the invention. 'invention. The various adjuvants are employed in proportions usually used in the field of cosmetics, for example from 0.01 to 20% of the total weight of the composition.

  According to this variant embodiment, the weight concentration of cromoglicic acid and / or its salts or esters will also range between 0.1 and 20% and preferably from 1 to 5% by weight of cromoglicic acid and / or a salt and or one of its esters. The concentration of gelling agent will vary from 0.1 to 10% of the total weight of the composition. Preferably, 0.5 to 5% hydroxyethylcellulose or 0.5 to 2% acrylic acid polymer will be used. While respecting these predefined percentages of concentrations for each constituent, the ratio of the weight concentrations between the cromoglicic acid and the gelling agent will preferably be between 2: 1 and 0.5: 1. According to a particularly simple and interesting mode, this ratio will be close to 1: 1. In these compositions, care will also be taken to maintain a sufficient amount of water to allow good dispersion of the constituents and avoid excessively high gel viscosity that could result.

  For application on particularly intolerant skin, it will preferably avoid the addition of perfume, alcohol, preservative and / or dye.

  The compositions according to the invention are in a form suitable for application to the skin, mucous membranes and / or integuments. In its simplest structure, ie consisting of water, cromoglicic acid and / or one of its salts and / or esters, of the gelling agent and optionally of an agent of appropriate pH, it is presented in the form of gel.

  According to the additional constituents, it may be used in the form of a gel, but also of lotion, in particular hair lotion, emulsion or dispersion, in particular of the oil-in-water or water-in-oil type, cream especially tinted cream, ointment, milk, mousse sticks (stick), especially in the form of lip balm, lipstick. To increase the fluidity of the compositions, it will then be used in particular mineral salts, complexons (EDTA) or silicone oils.

  The composition according to the invention may also be in a form suitable for oral administration. In particular, it may be in encapsulated form in soft capsules, or in absorbable gelled composition.

  In the case of a preservative-free composition, it will be preferable to present a daily individual dose form or a dispensing system including a protection such as a filter membrane, in order to avoid any bacterial contamination during the period of use. . Pump vials with filters, double-pocket vials or externally pressurized sprays may be used.

  According to the invention, the composition may contain, in addition, sun protection agents, especially for carrying out sun care, which may especially protect skins prone to sun allergies. It will then be possible to use, as sunscreen agent, organic and / or inorganic filters such as, for example, micronized particles of metal oxide, in particular of titanium oxide, iron oxide, cerium oxide, aluminum, etc. or metal silicate particles. The physico-chemical characteristics of the filter used and its concentration are dictated by the type of skin on which the composition will be applied, the degree of sun protection to be provided, and the desired final consistency of the composition, in accordance with the invention.

  According to the present invention, examples of hydrophilic or lipophilic active agents are vitamins, moisturizing agents such as hyaluronic acid, emollients, anti-free radical protection agents such as tocopherol acetate, cicatrizing agents such as allantoin, local analgesics such as bisabolol, other topical anti-inflammatory agents such as steroids, enoxolone, topical antihistamines, cutaneous antibiotics, local antiseptics such as benzododecinium bromide or zinc, calendula extract, soothing agents and mixtures thereof.

  As an emulsion, the composition may further contain fatty substances such as vegetable or animal fats, natural waxes, especially as a softening agent.

  As dyes that may be used according to the invention, liposoluble dyes such as R-carotene, Sudan brown, DC Red 17 and quinoline yellow may be mentioned in particular.

  As nacres usable according to the invention, there may be mentioned micas coated with natural oxides and pigments, or cholesterol esters.

  As pigments that can be used according to the invention, mention may be made especially of mineral pigments such as zinc, iron and cerium oxides and lacquers usually used such as shellac.

  The composition according to the invention can be produced in the usual manner. The cromoglicic acid and / or a salt thereof and / or an ester thereof will be dissolved or dispersed in water or an aqueous vehicle. The gelling agent is then added to the cromoglicate solution. To facilitate gel formation, the gelling agent may be separately dissolved in an aqueous vehicle prior to incorporation into the cromoglicate solution. The whole will be homogenized. Other constituents will then optionally be added in order to give the desired consistency and properties to the composition. The pH regulating agent, when necessary, will be added at the end, so that gelling takes place only at this stage of the formulation, so that the composition is well homogeneous.

  The invention also relates to the use in cosmetics of the abovementioned compositions for the care and / or treatment and / or protection and / or makeup and / or comfort and / or well-being of the skin and / or integuments and / or mucous membranes in humans and / or animals.

  The composition may be used for the make-up of the skin, in particular the lips, eyelids, eyes, in particular in the form of lipstick, eyeshadow, tinted cream, but also for the make-up or coloring of the dander on contact with the skin. particular eyelashes in particular in the form of mascara cream, eyebrows and hair to prevent allergic reactions to dyes or preservatives that these compositions contain.

  The compositions according to the invention find use in the cosmetic field by soothing, preventing and / or masking the unsightly reactions of the skin, skin appendages and / or mucous membranes such as redness, peeling, irritation, swelling and uncomfortable manifestations related to particularly to sensitivity reactions.

  The subject of the invention is also the use in the pharmaceutical field, and in particular in dermatology, of the compositions previously described, for producing a medicament intended to prevent and / or treat, by topical application and preferably cutaneous application, the manifestations of skin, nasal and / or ocular intolerance and sensitivity such as irritation, itching, swelling and / or allergic reactions and / or atopic diseases of the skin and / or skin areas in contact with the integuments and / or mucous membranes. Thanks to the local antiallergic effect of cromoglicic acid or its salts or esters, the compositions according to the invention are thus particularly suitable for producing a medicament intended, by oral application, to the symptomatic treatment of digestive disorders of allergic origin. and / or by topical and especially cutaneous application, to the symptomatic treatment of cutaneous, nasal and ocular allergic diseases.

  In addition, the compositions according to the invention are particularly suitable for cosmetic or dermatological use on dry, sensitive, intolerant, reactive or hypersensitive skin, allergic-type skin no longer supporting cosmetics, baby skin, naturally drier and more fragile skin irritated by a therapeutic treatment, external agents including shavings, epilations, aggressive climatic agents, the skin of elderly drier or finally all areas of skin that require specific care.

  By minimizing the risk of irritation, sensitization, skin reactions, nasal, ocular, or digestive allergic origin, this composition can perfectly serve as a basis for the realization of a cosmetic or pharmaceutical and especially dermatological hypoallergenic. The combination of the two components, cromoglicic acid and gelling agent, is compatible with a large number of active ingredients and therefore can easily be used as a structurant, thickener, at a concentration of 0.1 to 20%, to increase skin tolerance, nasal , ocular or digestive of a cosmetic or pharmaceutical and especially dermatological composition.

  The invention further relates to a cosmetic treatment method for sensitive, hypersensitive, intolerant or atopic skin or for the ocular and nasal mucous membranes of applying to a skin, mucous membrane or anther layer concerned, a composition according to the invention for the care, and / or the cosmetic treatment and / or the prevention of sensitization reactions and allergic skin, nasal or ocular manifestations in humans and / or animals.

  The compositions in their simplest structure, ie in the form of a hydrogel constituted by cromoglicic acid and / or one of its salts and / or esters and the gelling agent, optionally combined with a pH-regulating agent , show no toxicity and cause no local intolerance. They are not allergenic either.

  The following examples are presented to illustrate the invention and should in no way be considered as a limit to the scope of the invention. Unless otherwise stated, the concentrations are given as a percentage based on the total weight of the composition.

  Comparative Tests The level of active ingredient likely to pass the cutaneous barrier can be evaluated in an in vitro model on so-called Franz static diffusion cells. This kinetic and quantitative method consists in measuring the quantity of formulation passing through a membrane placed in a static diffusion cell, called Franz cell.

  - Procedure: A synthetic or porcine membrane is installed and maintained horizontally so as to delimit two compartments of Franz's cell. The lower compartment is filled with 0.9% sodium chloride solution to form a survival liquid or receptor phase of the diffused cromoglicate fraction. The upper compartment rests on the upper face of the membrane thus circumscribing a precisely defined surface.

  The assembly is thermostated at 37 C, and the areas of contact with the membrane are free of air bubbles. At the initial time, a precise amount of the tested formulation is applied to the upper surface of the membrane. The cromoglicate present in the survival liquid is assayed by high performance liquid chromatography.

  Results: The formulation tested showed particularly interesting results, in accordance with the invention.

  II Examples of cosmetic compositions according to the invention: In the examples and preparations, the proportions indicated are percentages by weight / total weight.

  A soothing aqueous gel for intolerant skins-Composition: sodium cromoglicate 2.00% Natrosol 250 HX pharm 2.00% (hydroxyethylcellulose / Hercules MSDS Inc.) purified water qs 100 -Protocol for the preparation of a 2000g gel: 1) A quantity of 40 g of sodium cromoglicate is dissolved in 1600 g of purified water. 2) A quantity of 40 g of Natrosol 250HX pharm is dispersed in 200 g of water. The solution obtained is poured into the cromoglicate solution. The whole is mixed until complete dissolution.

  3) The purified water is added to supplement the weight of 2000g.

  Other components can be added between step 2 and step 3 at the usual concentrations. It may especially be a preservative agent (nipagine), a perfume agent (rose water), a vegetable dye (crushed orange peel).

  Hydrogel calming irritated skin -Composition: Sodium cromoglicate 1.80% Carbopol 980NF 0.80% (acrylic polymer / BF Goodrich.) Triethanolamine qs pH 7 purified water qs 100 -Protocol for the preparation of a solution of 1000g: 1) A quantity 18 g of sodium cromoglicate is dissolved in 800 g of purified water. 2) A quantity of 8 g of Carbopol 980NF is dispersed in 200 g of water and the gel formed is mixed with the sodium cromoglicate solution until complete homogenization.

  3) The pH is adjusted to 7 by addition of triethanolamine.

  4) The purified water is added to supplement up to 1000g.

  After standing, the gel is divided into a sterile single-dose container of 1 g. It is also possible to add other components between step 2 and step 3, at the usual concentrations.

  Excipient for hypoallergenic cosmetic product Excipient: Disodium cromoglicate 2.00% Carbopol 980NF 0.80% (acrylic polymer / BF Goodrich.) Triethanolamine qs pH 7 purified water qs 100 -Protocol for the preparation of a composition of 2000g: 1) A quantity of 20 g of sodium cromoglicate is dissolved in 800 g of purified water. 2) A quantity of 8 g of Carbopol 980NF previously dissolved in 600 g of water is incorporated in the cromoglicate solution.

  3) The purified water is added to supplement the weight of 1000 g to form the excipient mixture.

  4) The excipient is incorporated, cold, in a moisturizing aqueous cosmetic composition at a concentration of 10% by total weight.

  5) At the final stage, the pH is adjusted to 7 by addition of triethanolamine. The composition is fluidized by adding silicone oils.

  III Examples of dermatological compositions according to the invention: In the examples and preparations, the proportions indicated are percentages by weight / total weight.

  Dermal composition for the treatment of atopic diseases Composition: sodium cromoglicate 1.00% Carbopol 980NF 0.80% (acrylic polymer / BF Goodrich.) Triethanolamine qs pH 7 purified water qs 100 -Protocol for the preparation of a 2000g composition: 1) An amount of 20 g of sodium cromoglicate is dissolved in 800 g of purified water. 2) An amount of 8 g of Carbopol 980NF previously dissolved in 500 g of water is incorporated and dissolved. 3) The pH is adjusted to 7 by addition of triethanolamine.

  4) Purified water is added to supplement up to 2000g.

Claims (17)

CLAIMS:   A pharmaceutical or cosmetic composition containing at least cromoglicic acid and / or a salt thereof and / or esters and a gelling agent selected from the group consisting of a hydroxyalkylcellulose, an acrylic acid polymer and their mixtures, in an aqueous vehicle.   2. Pharmaceutical or cosmetic composition according to claim 1 characterized in that the gelling agent is hydroxyethylcellulose.   3. Pharmaceutical or cosmetic composition according to one of claims 1 to 2, characterized in that the cromoglicic acid and / or a salt thereof and / or esters is present at a concentration of 0.1% to 20% by total weight. of the composition.   4. Pharmaceutical or cosmetic composition according to claim 3, characterized in that it contains sodium cromoglicate.   5. Pharmaceutical or cosmetic composition according to one of claims 1 to 4, characterized in that the gelling agent is present at a concentration of 0.1% to 10% by total weight of the composition.   6. Pharmaceutical or cosmetic composition according to one of the preceding claims, characterized in that the aqueous composition consists only of cromoglicic acid and / or a salt and / or ester thereof, gelling agent and an agent. of appropriate pH.   7. Pharmaceutical or cosmetic composition according to one of claims 1 to 5, characterized in that it contains the gelling agent at a concentration of 0.1% to 10% by total weight of the composition, in vehicles or diluents, pharmaceutically and / or or cosmetically acceptable.   8. Pharmaceutical or cosmetic composition according to one of claims 1 to 7 characterized in that it is in a form suitable for application to the skin.   9. Pharmaceutical or cosmetic composition according to one of claims 1 to 8, characterized in that it is in gel form.   10. Pharmaceutical composition according to one of the preceding claims intended, by topical application to the symptomatic treatment of cutaneous, ocular, nasal and / or oral application, to the symptomatic treatment of digestive disorders, allergic origin.   11. Use of a pharmaceutical or cosmetic composition according to one of the preceding claims for the production of products intended to prevent and / or reduce the manifestations skin, nasal, digestive and / or ocular uncomfortable, unsightly or painful skin, mucous membranes and / or sensitive, hypersensitive, intolerant or atopic dander.   12. Use of a composition according to one of the preceding claims for the production of a cosmetic product for the care, treatment, protection, makeup, comfort and / or well being of the skin, mucous membranes and / or dander.   13. dermatological use of a composition according to one of claims 1 to 9 for the production of a medicament intended, by topical application, to prevent and / or treat manifestations of intolerance and sensitivity of the skin, nose, and / or or oculars.   14. The dermatological use of a composition according to one of claims 1 to 9 for the production of a medicament intended, by topical application, to the symptomatic treatment of cutaneous, nasal and ocular disorders and / or by oral application to the symptomatic treatment of digestive disorders, of allergic origin.   15. Use according to one of claims 11 to 14 of a composition according to one of claims 1 to 10 in cutaneous application.   16. Use of a composition according to claim 6 as a structuring agent for increasing the cutaneous, nasal, digestive or ocular tolerance of a cosmetic or pharmaceutical composition.   17. Cosmetic treatment method for sensitive, hypersensitive, intolerant or atopic skin consisting in applying to a skin, mucous membrane and / or dander concerned area, the composition according to one of claims 1 to 9 for the care and / or or the cosmetic treatment and / or the prevention of sensitization reactions and allergic skin, nasal and / or ocular manifestations in humans and / or animals.