MXPA97010475A - Use of at least one beta-adrenergic agonist as an antagonist of substance - Google Patents

Abstract

The present invention relates to the use of at least one beta-adrenergic agonist in a cosmetic composition as substance P antagonist or for the preparation of a pharmaceutical composition, more particularly dermatological, intended to treat disorders associated with an excess of synthesis and / or release of substance P. The invention also relates to a cosmetic or pharmaceutical composition, for topical use, comprising at least one beta-adrenergic agonist and a cosmetic treatment procedure with a view to diminishing the pain related to an excess of synthesis and / or release of substance P or decrease the irritant effect of a cosmetic composition.

Description

USE OF AT LEAST ONE BETA-ADRENERGIC AGONIST AS AN ANTAGONIST OF SUBSTANCE P.

The present invention relates to the use of at least one β-adrenergic agonist in a cosmetic composition as substance P antagonist or for the preparation of a pharmaceutical composition, more particularly dermatological, intended to treat disorders associated with an excess of synthesis and / or release of substance P. The invention also relates to a cosmetic or pharmaceutical composition for topical use, containing at least one β-adrenergic agonist. The invention finally relates to a method of cosmetic treatment with a view to diminishing the pain related to an excess of synthesis and / or release of substance or to diminish the irritant effect of a compound, characterized in that it is applied on the skin, on the hair and / or on the mucous membranes a composition comprising a β-adrenergic agonist. There are polypeptides in mammals that belong to the family of tachykinins that induce smooth contractions in smooth muscle fibers. Among the compounds of this family, mention may be made of neurokinin ß, neurokinin a and substance P. Substance P is a polypeptide chemical element (a REF .: 26476 decapeptide), elaborated and released by a nerve ending. The location of substance P is specific to the neurons, both in the central nervous system and in the organs of the periphery. Thus, numerous organs or tissues receive afferents from neurons of substance P, are treated paricularly of the salivary glands, the stomach, the pancreas, the intestine (in this case, the distribution of substance P overlaps the intrinsic nerve plexus of Meissner and of Auerbach), of the cardio-vascular system, of the thyroid gland, of the skin, of the iris and of the ciliary bodies, of the bladder and evidently of the central and peripheral nervous systems. Due to the ubiquitous distribution of substance P, numerous disorders are associated with an excess of synthesis and / or substance P release. Substance P intervenes particularly in the transmission of pain and in diseases of the central nervous system (for example anxiety, psychosis, neuropathies, neurodegenerative disorders of the senile dementia type of Alzheimer's, dementia of the synosis, Parkinson's disease, Down syndrome, Xorsakoff syndrome, multiple sclerosis, schizophrenia), in respiratory diseases (such as, for example, bronchopneumonia) and inflammatory (such as for example rheumatoid polyarthritis), in allergic syndromes (such as for example asthma, allergic rhinitis, allergic pharyngitis, urticaria, eczematous dermatitis), in gastrointestinal diseases (such as for example ulcers, colitis, Crohn's disease), in skin disorders (such as, for example, psoriasis is, prurinous diseases, herpes, photodermatosis, atopic dermatitis, contact dermatitis, lichen, prurigo, pruritus, especially solar erythema, insect bites), in fibrosis and other alterations of the maturation of collagens (such as, for example, scleroderma), in cardiovascular disorders, in vasospastic alterations (such as, for example, migraines, Reynaud's disease), in immunological disorders, in disorders of the urinary tract (such as, for example, incontinence, cystitis), in rheumatic diseases, in some dermatological diseases and in ophthalmological conditions (such as, for example, conjunctivitis, uveitis, ocular itching, eye pain, irritation). The use of substance P antagonist is one of the effective therapeutic alternatives in all the conditions mentioned above. By substance P antagonist is meant any compound capable of partially or even completely inhibiting the biological effect of substance P.

Particularly, for a substance to be recognized as an antagonist of substance P it must induce a coherent pharmacological response (including or not its attachment to the substance P receptor) particularly in one of the following tests: the antagonist substance must decrease the extravasation of plasma through the vascular wall induced by capsaicin or by antidrhythmic nerve stimulation, or - the antagonist must cause an inhibition of smooth muscle contraction induced by the administration of substance P. Up to now Substance P antagonists are used to treat the disorders indicated above. The applicant has just discovered that β-adrenergic agonists respond to the criteria of substance P antagonist. Thus, the invention relates to the use of at least one β-adrenergic agonist as a substance P antagonist in a cosmetic composition. The invention also relates to the use of at least one β-adrenergic agonist for the preparation of a pharmaceutical composition intended to treat disorders associated with an excess of synthesis and / or substance release. Preferably in the pharmaceutical composition, the agonist β-adrenergic acid is used as substance P antagonist. Preferably, the compositions of the invention are intended for topical use. The present invention also relates to a cosmetic treatment process, characterized in that it uses a cosmetic composition defined according to the invention. The β-adrenergic agonists are sympathetic molecules that reproduce the stimulation effects of the sympathetic nerves. Sympathomimetics act on smooth muscle fibers. The prototype is adrenaline. Different receptors of a different nature (a or ß) and sympathomimetics are more active in certain receptors than in others. This is the case of ß-adrenergic agonists (they themselves subdivide into two main sub-types Bi and B2) - Compositions containing a β-adrenergic agonist have been described for the treatment of excess fat in the human body (EP- A-120165) or for the treatment of psoriasis (US 4038417) or also as an agent usable in baths to provide the skin with a feeling of freshness and the body a sensation of heat (JP-A-07258067). However, none of the prior art documents describe or suggest the involvement of substance P in the conditions that the compositions described are intended to combat and even less any relationship between substance P and β-adrenergic agonists. The use of β-adrenergic agonists as a substance P antagonist has never been described. Among the β-adrenergic agonists which can be used according to the invention, mention may be made of salbutamol, isoproterenol, CGP-12177, nilidrine, saimeterol, fenoterol, terbutaline or pirbuterol. Preferably, according to the invention, the = albuta ol is used. The amount of β-adrenergic agonist usable according to the invention is well understood depending on the effect sought and the nature of the agonist used. By way of illustration, according to the invention, the agonist can be used in a weight amount representing 10-? Or 10% of the total weight of the composition and preferably in an amount representing from 10% to 4% of the weight total of the composition. The examples of cutaneous disorders related to an excess of synthesis and / or of release of substance P have been previously seen in the text. Thus, the invention more particularly aims at the use of at least one β-adrenergic agonist in a cosmetic composition. or for the preparation of a pharmaceutical composition intended to treat skin disorders such as, for example, psoriasis, pruriginous diseases, urticaria, dermatitis a opicas, contact dermatitis, fibrosis., alterations in the maturation of collagen and, in a general way, pruritic and / or erythematous dermatoses. On the other hand, in the field of skin disorders it is known that certain skins are more sensitive than others. At this increased sensitivity, phenomena such as skin irritations and / or herpes and / or erythemas and / or sensations of dysesthesia and / or irritation sensations and / or pruritus of the skin and / or mucous membranes are often associated. However the symptoms of sensitive skins were so far poorly characterized and the problem of these skins was, in fact, poorly defined. In fact, nobody knew exactly the process produced in the sensitivity of the skin. Some thought that a sensitive skin was a skin that reacted to cosmetic products, others that it was a skin that reacted to several external factors, not necessarily related to cosmetic products. Sensitive skins were also assimilated with allergic skins. The tests have been put in place to delimit the sensitive skins, for example tests with lactic acid and with DMSO which are known to be irritating substances: see for example the article by K. Lammintausta et al., Dermatoses, 1988, 36, pages 45-49, and the article by T. Agner et J. Serup, Clinical and Experimental Dermatology, 1989 14, pages 214-217. Due to the ignorance of the characteristics of the sensitive skins, until now it was very difficult even impossible to treat them. In fact, they were treated indirectly, for example, by limiting the use of irritants such as surfactants, preservatives or perfumes, or the use of certain cosmetic or dermatological active agents in cosmetic or dermatological compositions. After numerous clinical trials, the applicant firm has been able to determine the symptoms related to the "sensitive feet." These symptoms are in particular subjective signs, which are essentially dysesthetic sensations.Dysesthetic sensations are understood as more or less painful sensations felt in an area. skin like itching, tingling, itching or itching, burns, irritations, restlessness, tightness, etc. The applicant firm has also been able to show that a sensitive skin was not an allergic skin, in fact, an allergic skin is a skin that reacts with a external agent, an allergen, which triggers an allergy reaction.It is an immunological process that only occurs when allergen is present and that only affects sensitized subjects.The essential characteristic of sensitive skin is according to the applicant , on the contrary, a mechanism of response to external factors, which may affect to any individual, even if the so-called sensitive skin individuals react to them more quickly than the others. This mechanism is not immunological, it is aspecific. The Applicant firm has found that sensitive skins can be divided into two large clinical forms, irritable and / or reactive skins and leathers. An irritable and / or reactive skin is a skin that reacts by itching, that is by itching or itching, with different factors such as the environment, emotions, food, wind, friction, the razor, the soap, surfactants, hard water with strong calcareous concentration, temperature variations or wool. In general, these signs are associated with dry skin with or without herpes, or with a skin that has an eyelid. An intolerant skin is a skin that reacts by sensations of irritation, tightness, tingling and / or spots r.-jds, to different factors such as the environment, emotions, food and certain cosmetic products. In general, these signs are associated with a hyperseborrhoeic or acneic skin with or without herpes, and an erythema. "Sensitive" scalps have a more univocal clinical semiology: the sensations of pruritus and / or itching and / or irritation are essentially triggered by local factors such as friction., soap, surfactants, hard water with a strong limestone concentration, shampoos or lotions. These sensations are also triggered sometimes by factors' such as the environment, emotions and / or food. An erythema and a hyperseborrhea of the scalp as well as a peculiar state are frequently associated with the preceding signs. On the other hand, in certain anatomical regions with large wrinkles (inguinal, genital, axillary, popliteal, anal, "sub-mammary, elbow wrinkles) and feet, sensitive skin is translated by prurient sensations and / or dysesthetic sensations (irritations, itching) related in particular to sweat, friction, wool, surface-active agents, certain cosmetic preparations, hard water with a high calcareous concentration and / or variations in temperature. Whether the skin is sensitive or not, the applicant has also set up an assay, and after having carried out a large number of tests in order to define a sensitive skin, it was found that a relationship between skin-colored people and reacting them to a topical application of 5. The test with capsaicin consists of applying on about 4 cm2 of skin 0.05 ml of a cream containing C .075% of capsaicin and in observing the appearance of subjective signs caused by this appearance, such as itching, irritation and itching. In subjects with sensitive skin, these signs appear between 3 and 20 minutes after application and are followed by the appearance of an erythema that begins in the periphery of the application area. Until now, capsaicin was used as a medicine, in particular to treat the pains of the area. Capsaicin causes a release of the neuropic peptides, and in particular the tachykinins that come from the nerve endings of the epidermis and the dermis. The Applicant has observed that the common physiological scheme of all states of sensitive skin was related to a great ability to release tachykinins and more particularly substance P in the skin. The dysesthetic manifestations that are caused by their release are called "neurogenic". No one had established a relationship between substance P and sensitive skin. The clinical signs of sensitive skin are essentially subjective: itching, tingling, pruritus, tightness, irritation, and sometimes associated with erythema. These signs are due to non-specific external factors. The symptoms appear essentially localized in the face, in the neck and in the scalp, but they can also appear throughout the body. Thus, the applicant has discovered that one of the essential characteristics of sensitive skin is related to the release of substance P and therefore that the use of substance P antagonists may allow a preventive and / or curative effect of sensitive skin. . In order to treat sensitive skin, the Applicant has therefore considered using substance P antagonists. Indeed, it has surprisingly observed that the incorporation of a substance P antagonist in a composition intended for topical use makes it possible to avoid irritation and / or irritation. the dysesthetic sensations and / or the pruritus of the skin. The invention thus relates more particularly to the use of at least one β-adrenergic agonist in a cosmetic composition or in the preparation of a pharmaceutical composition, these compositions being intended to treat sensitive skin. The present invention still more particularly aims to use at least one β-adrenergic agonist in a cosmetic composition or for the preparation of a pharmaceutical composition, these compositions being intended to prevent and / or to combat skin irritations and / or herpes and / or erythemas and / or sensations of irritation and / or dysesthesia and / or pruritus of the skin and / or mucous membranes. The β-adrenergic agonist can be used in a composition that must be ingested, injected or preferably applied to the skin (in all skin areas of the body), hair, nails or mucous membranes (buccal, malar, gingival, genital,? inal, conjunctive). Depending on the form of administration, this composition can be present in all galenic forms that are badly used. For injection, the composition may be in the form of an aqueous lotion, oily suspension or in the form of a serum. For the eyes, it can be in the form of drops and for ingestion, it can be in the form of capsules, granules, syrups or tablets. More particularly, the β-adrenergic agonist is used in a composition for topical use. The subject of the invention is also a cosmetic or pharmaceutical composition, for topical use, comprising at least one β-adrenergic agonist. For a topical application on the skin, the composition can have the particular form of aqueous solution or oily suspension or dispersion of the lotion or serum type, of liquid or semi-liquid milk-like emulsions, obtained by dispersing a phase fat in an aqueous phase (H / E) or vice versa (E / H), or of suspensions or emulsions of a soft consistency of the aqueous or anhydrous cream or gel type, or even of microcapsules or microparticles or vesicular dispersions of the ionic type and / or non-ionic. These compositions are prepared according to the usual methods. These can also be used for hair hydroalcoholics, or in the form of creams, gels, emulsions, foams or even in the form of aerosol compositions also containing a pressurized propellant. The amounts of the different constituents of the compositions according to the invention are those conventionally used in the domains considered. These compositions are in particular cleaning, protective, treatment or care creams for the face, for the hands, for the feet, for large anatomical folds or for the body (for example day creams, night creams, make-up creams, make-up creams, anti-sun creams), fluid foundation, make-up milk, body care or care milks, sunscreen milk, lotions, gels or foams for skin care, such as cleaning lotions, sunscreen lotions. artificial tanning lotions, bath compositions, deodorant compositions containing a bactericidal agent, gels or aftershave lotions, epilating creams, anti-insect bite compositions, anti-pain compositions, compositions for treating certain skin diseases such as eczema , rosaduras, psoriasis, lichen, severe itching. The compositions may also consist of solid preparations consisting of soaps or sticks of 1 impiety. The compositions can also be packaged in the form of an aerosol composition also containing a pressurized propellant. The β-adrenergic antagonist used according to the invention can also be incorporated in various compositions for hair care, and particularly shampoos, lotions, marking lotions, treatment lotions, creams or gels for combing, dye compositions (in particular dyes) oxidation) optionally in the form of coloring shampoos, restructuring lotions for hair, permanent compositions (in particular compositions for the first stage of a permanent), lotions or gels against hair loss, shampoos aptiparasi tar, etc. The compositions can also be of buco-dental use,? O? example a toothpaste. In this case, the compositions may contain customary adjuvants and additives for compositions for oral use and in particular lens-active agents, thickening agents, wetting agents, polishing agents such as silica, various active ingredients such as fluorides, in particular fluoride. of sodium, and optionally sweetening agents such as sodium excretion. When the composition is an emulsion, the proportion of the fatty phase can range from 5% to 80% by weight, and preferably from 5% to 50% by weight with respect to the total weight ie the composition. The oils, waxes, emulsifiers and co-emulsifiers used in the composition in the form of an emulsion are chosen from those conventionally used in the cosmetic domain. The emulsifier and co-emulsifier are present, in the composition, in a proportion ranging from 0.3% to 30% by weight, and preferably from 0.5 to 20% by weight with respect to the total weight of the composition. The emulsion may also contain lipid vesicles. When the composition is an oily gel or solution, the fatty phase may represent more than 90% of the total weight of the composition. In a known manner, the cosmetic composition may also contain adjuvants customary in the cosmetic domain. such as hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic additives, preservatives, antioxidants, solvents, perfumes, fillers, filters, odor absorbers and coloring materials. The amounts of these various adjuvants are those conventionally used in the cosmetic domain, and for example from 0.01% to 10% of the total weight of the composition. These adjuvants, according to their nature, can be introduced in the fatty phase, in the aqueous phase and / or in the lipid spherules. As oils or waxes useful in the inventionMention may be made of mineral oils (petrolatum oil), vegetable oils (liquid fraction of shea butter, sunflower oil), animal oils (perhydrosqualene), synthetic oils (Purcellin oil), silicone oils or waxes ( cyclomethicone) and fluorinated oils (perfluoropolyethers), beeswax, carnauba or paraffin waxes. It is possible to add to these oils fatty alcohols and fatty acids (stearic acid). Emulsification is useful in the invention, for example, glycerol stearate, polysorbate 60 and the mixture PEG-6 / PEG-32 / Glycol Stearate sold under the name of Tefose® 63 by the Gettefosse company. As solvents useful in the invention, there may be mentioned minor alcohols, in particular ethanol, isopropanol and propylene glycol. As hydrophilic gelling agents useful in the invention, mention may be made of carboxyvinyl polymers (carbomer), acrylic copolymers such as copolymers of acrylates / alkylacrylates, iocylaminides, polysaccharides such as hydroxypropylcellulose, gums natural and clays, and, as lipophilic gelling agents, mention may be made of modified clays such as benthones, metal salts of fatty acids such as aluminum stearates and hydrophobic silica, ethylcellulose, polyethylene. The composition may contain other active hydrophilics such as proteins or protein hydrolysates, amino acids, poiols, urea, allantoin, sugars and sugar derivatives, water-soluble vitamins, plant extracts and hydroxy acids. As active lipophilic, retinol can be used (vitamin A) and its derivatives, tocopherol (vitamin E) and its derivatives, essential fatty acids, ceramides, essential oils, salicylic acid and its derivatives. According to the invention, it is possible, if possible, to associate at least one β-adrenergic agonist with other active agents intended in particular for the prevention and / or treatment of cutaneous affections. Among these active agents, mention may be made, by way of example: - agents that modulate differentiation and / or proliferation and / or skin pigmentation such as retinoic acid and its isomers, retinol and its esters, vitamin D and its derivatives, tai estrogens such as estradiol, kojic acid or hi roquinone; antibacterials such as phosphate of cliamide, erythromycin or antibiotics of the class of tetracyclines; antiparasitic agents, in particular, metroindazole, crotamiton or pyrethrinoids; - anti fungal, in particular compounds belonging to the class imidazoles such as econazole, ketoconazole or miconazole or their salts, polyene compounds, such as amphotepsin B, compounds of the family of amines and sheets, such as terbinafine, or n octop .irox; - antiviral agents such as acyclovir; - steroidal anti-inflammatory agents, such as hydrochloride tizonamethasone valerate or clobeta propionate = cl, or nonsteroidal anti-inflammatory agents such exile ibuprofen and its salts, diclofenac and its salts, acetylsalicylic acid, acetaminophen or glycyrrhetinic acid; anesthetic agents such as lidocaine hydrochloride and its derivatives; antipruritic agents such as tenaldine, trimeprazine or cyproheptadine; - Ceratolytic agents such as alpha- and beta-hydroxycarboxylic acids or beta-ketocarboxylic acids, their salts. amides or esters and more particularly hydroxy acids such as glycolic acid, lactic acid, icic acid. citric acid and, in general, fruit acids, and n-octane-5-salt; - anti-free radical agents, such as alpha-tocopherol or its esters, superoxide dismutases, certain metal chelators or ascorbic acid and their esters; - anti-seborrheic drugs such as progesterone; - anti-pellets such as octopirox or zinc pyrithione; - anti-acne drugs such as retinoic acid or bezoi peroxide. Thus, according to a particular embodiment, the invention relates to the use of at least one β-adrenergic agonist at least one agent selected from antibacterial, antiparasitic, antifungal, antiviral, antiinflammatory, antipruritic, anesthetic, ceratogenic agents. , anti-free radicals, anti-seborrheic, anti-1, anti-acne and / or agents that modulate differentiation and / or proliferation and / or cutaneous pigmentation. Advantageously, according to the invention at least one β-adrenergic agonist can be associated with irritant effect products commonly used in the cosmetic or pharmaceutical field, products that are sometimes cosmetic and pharmaceutical active agents. The presence of a substance P antagonist in the form of at least one β-adrenergic agonist in a cosmetic or pharmaceutical composition comprising a product having an irritant effect makes it possible to substantially attenuate or even suppress this irritant effect. This also makes it possible to increase the amount of active principle of irritant effect in relation to the amount of active principle normally used, in view of an improved efficiency. Thus the invention also relates to a cosmetic or pharmaceutical composition, preferably for topical use, which comprises in a cosmetically or pharmaceutically acceptable medium at least one product with an irritant effect, characterized in that it also contains at least one β-adrenergic agonist.

Examples of irritant products which may be mentioned are surfactants (ionic or non-ionic), preservatives, organic solvents or active agents such as a-hydroxy-acids (citric acid)., malic, glycolic, tartaric, mandelic, lactic), the ß-hydroxyacids (the acidic salt and its derivatives), the a-ketoacids, the ß-ketoacids, the retinoids (retinal, retinal, retinoic acid), anthralines (dioxiantranol), anthranoids, peroxides (particularly benzoyl), mincxidil, lithium salts, antimetabolites, vitamin D and its derivatives, dyes or hair dyes iparaíeni lepdiamina yso derivatives, aminophenols), perfumed alcoholic solutions (perfumes, cologne waters, aftershave lotions, deodorants), antiperspirant agents (some aluminum salts), depilatory or permanent active agents (thiols), depigmenting active agents (hydroquinone). The use of substance P antagonist makes it possible in particular to multiply by 2 to 10 times the amount of active principle of irritant effect in relation to the state of the art, without feeling all the discomforts mentioned above. Thus, hydroxy acids up to 50% by weight of the composition or retinoids can be used up to 5%, notably decreasing their irritant nature.

In these compositions, the β-adrenergic agonist can be used preferably in an amount ranging from 10% to 10% by weight with respect to the total weight of the composition, and in particular in an amount ranging from -! 5% to 4% by weight with respect to the total weight of the = > i • _ _, n. Of course, the compositions according to the invention comprising, in a cosmetically or pharmaceutically acceptable medium, at least one product with an irritant effect and at least one β-adrenergic agonist can be present in any known pharmaceutical form, with, in particular, those described above in the text. . The subject of the present invention is also a cosmetic treatment process for the purpose of reducing the irritant effect of a compound, characterized by the fact that it is applied on the skin, on the hair, and / or on the mucous membranes, a composition which comprises at least one β-adrenergic agonist. The subject of the present invention is also a cosmetic treatment process for the purpose of reducing pain related to an excess of synthesis and / or substance P release, characterized in that it is applied on the skin, on the hair, and on the hair. / or on the mucous membranes a composition comprising at least one β-adrenergic agonist. These procedures of. Cosmetic treatment of the invention can be carried out in particular by applying the cosmetic compositions such as those defined above, according to the technique of usual use of these compositions. For example: application of creams, gels, serums, lotions, make-up or anti-soothing milks on the skin or on dry hair, application of a lotion for hair on wet hair, shampoos, or the application of toothpaste on the gums. The following examples illustrate the invention without limiting it in any way. In the compositions, the indicated proportions are percentages by weight, unless otherwise mentioned.

Example 1: Pharmacological activity of an ft-adrenergic agonist: In vivo functional assay on neurogenic inflammation model; An in vivo functional assay was performed on a neurogenic inflammation model to demonstrate the antagonistic nature of substance P 'of one of the β-adrenergic agonists, according to the method described by Xu X.J. and collaborators (Neuroscienceá, 1991, 42, 731-737). The test consists of provoking peurogenic inflammation by the antidrotic stimulation of the saphenous nerve in the anesthetized animal. This ner 'the hind legs. The stimulus causes release from the nerve endings of substance P, responsible in part for neurogenic inflammation. Neurogenic inflammation is quantified by measuring tissue permeability or Evans blue, a marker of tissue extravasation of plasma albumin that occurs during the course of inflammation. This reference model is used for the in vivo investigation of substance P antagonists.

The results of this study are summarized in the table given below. Those that represent the average of the results of 8 experiment.

Prod D act Conc 5.98 2.44 ± 0 n. d n.d 1.37 ± 0. 0.32 ± ? n t r .56 32 aci 0.65 .00 .00 7"95% bike on Est, p < 0.01 p < 0.001 p '0.001 p ^ O.001 p 0.001 i, díst icos A = Control (in the absence of any inhibitor) 3 = E = panty II: 30 nmol (Reference SP antagonists) C = Salbutamol: 1 μmol D = Isoproterenol. 1 μmol 2 E E = CGP12177, HCl. i μmol F = Nilidrine, HCl. 1 μmoles *. expressed in μg / ml Evans blue n.d. . not detected These results show that whatever the chemical structure of the different compounds of the ß-adrenergic agonist family, the group of these molecules exerts, always in a relatively important way, an activity of antagonist type of substance P.

Example 2: Dose effect of salbutamol in the antidromic stimulation model presented in example 1.Product Salbutamol Espanti da II Dosi: 0.1 1 nmo i 10 100 30 n l is nm l is n inha- 17 80 100% 57% i iiciCn Estada. s. p < 0.05 p'0.01 p < 0.01 p < 0.01 tico; no yes. -vir The results show that the activity of Salbutamol on the release of substance P is dose-dependent. They also show a very important activity, approximately 30 times higher than that of the reference molecule, the Spastide II.

Example: Examples of formulations illustrating the invention. These compositions have been obtained by simple mixing of the different components.

Composition 1: Antipruritic lotion: Salbu amo1 0.01% Antioxidant 0.05% Isopropanol 40.00% Conservative Water qsp 100% Composition 2: Gel for the treatment of psoriasis Sal u amo 1 0.10% Hydroxypropylcellulose (Klucel H 1.00% sold by the Hercules Company) Antioxidant 0.05% Isopropan l 40.00% Preservative- 0.30% Water qsp 100% Composition 3: Creída for the care of the face (emulsion of oil in water) Isoproterenol 0.50% Glycerol stearate 2.00% Polysorbate 60 (Tween 60 sold by 1.00% the ICI Company) Stearic acid 1.40% Triethanolamine 0.70% Carbomer 0.40% Liquid fraction of Karite butter 12.00% Ferhidroescuale or 12.00% Antioxidant 0.05% Perfume 0.50% Conservative 0.30% Water qsp 100% Composition 4: Shampoo a ~: 0 u: .c3: u 1 C.05% Lauryl ether sulfate Na (2.2 OE) Hydroxypropyl cellulose (Klucel H 1.00% sold by the Hercules company) Perfume 0.50% Conservator 0.30% Water qsp 100% Composition 5: Anti-pain gel Saibutamol 0.25% Hydroxypropylcellulose (Klucel H 1.00% sold by the Hercules Company) Antioxidant 0.05% Iidocaine hydrochloride 2.00% Isopropan l 40.00% Conservative 0.30% Water qsp Composition 6: Cream for the care of solar erythema (oil in water emulsion) Isoproterenol 0.001% Glycerol stearate 2.00% Foisorbate 60 (Tween 60 sold by 1.00% in the ICI company) Stearic acid 1.40% Glyretinic acid 2.00% Triethanolamine 0.70% Car omer, 0.40% Liquid fraction of Karite butter 12.00% Sunflower oil 10.00% Antioxidant '' 0.05% Fragrance . 0.50% Conservative 0.30% Water qsp 100% Composition 7: H / E emulsion for the treatment of facial skin Fat phase: Apricot kernel oil 14.50% (triglycerides of oleic-iinoleic acids) Liquid fraction of Karite butter 7.00% (Tpgl icéridos of palmitic acids- this rich-oleic-1 Inoléico) Propyl phorahydroxybenzoate 0.10% (conservative) Blend of fatty alcohol (Alcohol "1.00% stearyl, arachidyl alcohol, behenyl alcohol) sorbitan mono-stearate (Span 60 2.50% of ICI) Mixture of 2-ethyl hexanoate of 2.00% ceti lestearyl, isopropyl myristate (Purcellin oil) Aqueous phase '-conservatives 0.05% Disodium sai of ethylene di-amine 0.05% tetraacetic acid 2H = 0 (complexing) Neutral izante 0.50% 0.70% ificante gel Glycerin 5.00% 2.50% oxyethylenated sorbitan monostearate (20 OE) (ICI Tween 60) (surfactant) n-ostaniol-5-salicylic acid) 0% Salt butamo 1 Demineralized or permuted demineral water "qsp .00 Composition 8: H / E emulsion for the treatment of facial skin Fat phase: Almond oil of apricot 14.50% Liquid fraction of butter of Karite 7.00% (Tr igl icépdos of palmitic-acetic stea-oléico-li oleic acid) Propyl parahydroxybenzoate 0.10% (conservative) Fatty alcohol mixture (alcohol 1.00% stearic, arachidyl alcohol, behenyl alcohol) sorbitan mono-stearate (Span 60.50% ui-1) Mixture of 2.00% 2-ethyl hexanoate ceti iesteari lo, myristate of isopropyl (Purcellin oil) Aqueous phase Conservatives 0.05% Disodium salt of ethylene di-amine 0.05% tetraacetic acid 2H20 (adjuvants) Neutralizing 0.50% Gelifying 0.70% Glycerin 5.00% 2.50% sorbitan monostearate oxieti le ado (20 0E) (Tween 60 from ICI) (surfactant) 0.025% retinoic acid Salt butamo 0.05% Demineralized or permuted water 100% qep

Claims (16)

1. Use of at least one β-adrenergic agonist as a substance P antagonist in a cosmetic composition.

2. Use of at least one β-adrenergic agonist for the preparation of a pharmaceutical composition intended to treat disorders associated with an excess of synthesis and / or release of substance P.

3. Use according to claim 2, characterized in that the β-adrenergic agonist is used as substance P antagonist.

4. Use according to any of the preceding claims, characterized in that the composition is intended for topical use.

5. Use according to any of the preceding claims, characterized in that the composition is intended to treat skin disorders.

5. Use according to the preceding claim, characterized in that the composition is intended to treat psoriasis, pruritic diseases, urticaria, atopic dermatitis, contact dermatitis, fibroses, alterations in the maturation of collagen and in a general way Pruritic and / or erithematous dermatoses.

7. Use according to any of the preceding claims, characterized in that the cosmetic or pharmaceutical composition is intended to treat sensitive skins.

8. Use according to any of the preceding claims, characterized in that the cosmetic or pharmaceutical composition is intended to prevent and / or combat skin irritations and / or herpes and / or erythema and / or sensations of dysesthesia and / or sensations of irritation and / or pruritus of the skin and / or mucous membranes.

9. Use according to any of the preceding claims, characterized in that the β-adrenergic agonist is used in a weight amount representing 10 -?% To 10% of the total weight of the composition.

10. Use according to the preceding claim, characterized in that the β-adrenergic agonist is used in a weight amount representing from 1CT5% to 4% of the total weight of the composition.

11. Use according to any one of the preceding claims, characterized in that the β-adrenergic agonist is chosen from salbutamol, isoproterenol, CGP12177, nilidrine, salmeterol, fenoterol, terbutaline or pirbuterol.

12. Use according to the preceding claim, characterized in that the β-adrenergic agonist is salbutamol.

13. Cosmetic treatment procedure with a view to diminishing the pain related to an excess of synthesis and / or substance P release, characterized in that a composition is applied to the skin, on the hair, and / or on the mucous membranes comprising at least one β-adrenergic agonist.

14. Cosmetic treatment process with a view to reducing the irritant effect of a compound, characterized in that a composition comprising at least one β-adrenergic agonist is applied to the skin, on the hair, and / or on the mucous membranes.

15. A cosmetic or pharmaceutical composition comprising, in a cosmetically or pharmaceutically acceptable medium, at least one product with an irritant effect and at least one β-adrenergic agonist.

16. Cosmetic or pharmaceutical composition according to claim 15, characterized in that it is for topical use.