MXPA00008971A - Use of retinoic acid activity inhibitors to slow down hair loss - Google Patents

Abstract

The invention concerns the use in or for preparing acosmetic or pharmaceutical, preferably dermatological, composition, of at least a retinoic activity inhibitor, said composition being designed to slow down or preventing the growth of hairs and/or hair. Said composition is also designed to slow down loss of hairs and/or hair.

Description

USE OF INHIBITORS OF RETINIC ACID ACTIVITY TO DELAY HAIR LOSS DESCRIPTION OF THE INVENTION The present invention relates, in its most general aspect, to the use in a cosmetic composition or for the preparation of a pharmaceutical composition to delay or prevent the growth of hairs and / or hairs, at least an inhibitor of retinoic acid activity. The compositions according to the present invention are also intended to delay the fall of the hairs and / or the hair. The invention also relates to a method of non-therapeutic treatment for modifying the growth of hair. In the human being, the hair growth and its renewal are mainly determined by the activity of the hair follicles. Its activity is cyclic and essentially comprises three phases, namely the anagen phase, the catagen phase and the telogen phase. To the active anagen phase or growth phase, which lasts several years and in the course of which the hair grows, a very short catagen phase occurs and REF, 122555 transient that lasts a few weeks, then a resting phase, called telogen phase, which lasts a few months. At the end of the resting period, the hair falls out and another cycle begins again. The hair is therefore constantly renewed, and of the approximately 150,000 hairs comprising one hair, at each moment, about 10% of them are at rest and will therefore be replaced in a few months. In a significant number of cases, premature hair loss occurs in genetically predisposed subjects and it particularly affects men. It is more particularly about androgenetic or androgenic or even androgeno-genetic alopecia. This alopecia is essentially due to a disturbance of the capillary renewal that produces, in a first phase, the acceleration of the frequency of the cycles depending on the quality of the hair after its quantity. There is a progressive impoverishment of the hair by regression of the hair called "terminals" in the hair phase. There are areas that are preferentially affected, particularly the temporary or frontal gulfs in men and in women, a diffuse alopecia of the -vertex is observed. For many years now, in the cosmetic or pharmaceutical industry, substances have been sought to eliminate or reduce the effect of alopecia, and particularly to reduce hair loss or to induce or stimulate hair growth. With these aims, a large number of very diverse active substances or compounds have already been proposed. They will be cited among others to remember vitamins such as vitamin E, amino acids such as serine or methionine, vasodilators such as acetylcholine and its derivatives, female hormones such as estradiol, keratolytic agents such as salicylic acid or chemical compounds such as for example 2,4-diamino-6-pyperidinopyrimidine 3-oxide or "Minoxidil" described in US Pat. No. 4,596,812 or also its numerous derivatives as described, for example, in patent applications EP 353123, EP 356271, EP 408442, EP 522964, EP 420707, EP 459890, EP 519819. Mention may also be made of 6-amino-1,2-dihydro-1-hydroxy-2-imino-4-piperidino-pyrimidine and its derivatives, which are described more particularly in U.S. Patent No. 4,139,619.

It only remains, in a general way, that it would be interesting and useful to be able to have active substances different from those already known. Minoxidil, if it constitutes the reference compound in the field, presents not insignificant side effects that make its use delicate. The discovery of substances with an effect on the growth and / or hair loss without presenting annoying side effects remains a main objective of the investigation. On the other hand, it is interesting to find compounds that are likely to delay the growth of hairs and / or hair. It is known, in a general way, that all-trans retinoic acid acts on the differentiation and / or proliferation of cells interacting with nuclear receptors or RARs (Retinoic Acid Receptors) contained in the cell nucleus. Numerous synthetic structural analogs of all-trans retinoic acid or 9-cis-retinoic acid commonly called "retinoids" have been described to date in the literature. There are, nowadays, three identified sub-types of RAR receptors called respectively RAR-a, RAR-ß and RAR- ?. These receptors, after ligand binding (ie, all-trans retinoic acid), interact with the promoter region of genes regulated by retinoic acid at the level of specific response elements (RARE). Some analogs can be fixed and activate a particular RAR receptor subtype (ct, ß or?). Other analogues, finally, do not exhibit any particular selective activity with respect to these different receptors. In this respect, and for example, the all-trans retinoic acid activates the RARs (specific agonist ligand RARs), any confused subtype. Retinoic acid and retinoids in general, by binding with the RAR receptors that regulate the activity of RAR receptors, have been described as being able to treat numerous disorders or skin conditions, and more particularly alopecia. The retinoic acid antagonists will, on the contrary, inhibit the activity of the retinoic acid or its metabolites at the cellular level. It is more particularly the RAR antagonists that have just joined RAR receptors, but do not induce the activity observed for retinoic acid or retinoids. Thus, it has been shown that RARa receptor antagonists inhibit cell differentiation induced by retinoids on cells of the HL60 cell class or on the contrary reverse the inhibition of retinoid-induced mouse B-cell proliferation (C APFBL & col., Proc. Nati Acad. Sci. USA, 89, 1992, 7129-7133). Different retinoic acid antagonists are described in patent application EP 0 740,937. They have been recommended to treat alterations and / or conditions related to an up-regulation of RAR receptors and / or hypervitaminosis A that is most often translated by an inflammatory, allergic and / or immunological component, such as psoriasis. They have also been described as alopecia treators. Now, after important research, it has now been found by the applicant that by inhibiting the activity of retinoic acid within the skin cells in the vicinity of the hair follicles, it could, quite unexpectedly and surprisingly, be delayed by substantially the hair cycle and more particularly the anagen phase or the telogen phase. More precisely, it has been found that by inhibiting the activity of the retinoic acid, the growth of the hairs and / or the hair can be retarded and / or delayed and / or the hair and / or hairs can be delayed. This discovery forms the basis of the present invention. Thus, according to a first aspect of the present invention, the use is now proposed in or for the preparation of a cosmetic or pharmaceutical composition, preferably dermatological, intended to delay and / or prevent the growth of hairs and / or hairs , of at least one inhibitor of retinoic acid activity. In a second aspect of the invention, the use is now proposed in or for the preparation of a cosmetic or pharmaceutical composition, preferably dermatological, intended to delay the fall of the hairs and / or hairs, of at least one inhibitor of the activity of the retinoic acid. The inhibitors of the activity of the retinoóico acid can act according to two routes, first accelerating the cellular metabolism of the retinoic acid in order to diminish the cellular concentration of the latter, the second antagonizing its action at cellular level. The inhibitors of the activity of retinoic acid can therefore, according to the invention, be accelerators of the metabolism of retinoic acid or antagonists, inverse agonists or partial agonists of retinoic acid. By retinoic acid antagonists, compounds according to the invention which inhibit the action of retinoic acid and / or its metabolites and / or retinoids are preferably understood according to the invention. It is more particularly the RAR antagonists, which bind to the RAR receptors without activating them, however. The compounds which inhibit the activity of in vivo retinoic acid "selected according to the test described in the patent application EP 96 401 170 filed on May 31, 1996 on behalf of CIRD GALDERMA are understood more particularly. identifying RARS antagonist molecules, characterized in that it comprises the following steps: (i) a sufficient amount of an RAR agonist molecule is typically applied on a part of the skin of a mammal, (ii) it is administered systemically or topically on this same mammal or on this same part of the mammalian skin, before, during or after step (i) / a molecule capable of presenting an antagonistic activity of the RARs and (iii) the response on the part of Thus, when the molecule administered is an antagonist of the RARs, the thickness of the part of the treated skin of the mammal is increased by a molecule RAR agonist is not appreciated or decreased. An inhibition of the response is therefore observed. Practically, the mammal is a rodent such as a mouse, a rat, a guinea pig, a hamster or a rabbit. The part of the mammalian skin used can be from any part of the body of the mammal. The response on the part of the skin thus treated of the mammal to be evaluated corresponds to a clinical modification of this. Generally, this response to evaluate corresponds to a modification of the thickness of the part of the skin thus treated. The thickness measurement of the part of the skin thus treated can be carried out by any method known per se. When the part of the skin used is smooth, its thickness can be measured by folding it. In a more practical way, the skin of the ear is used. The measurement of the ear thickness can then be carried out by an oditest icometer. Well understood, the evaluation of the stage (iii) corresponds to a measurement of the response of the part of the skin thus treated and a comparison of this measurement with that of the response of this same part of the skin treated, under the same conditions, with the agonist molecule of the RARs alone. Preferably, the RAR agonist molecules are chosen from compounds capable of inducing the differentiation of the cells (F9) of mouse embryonic teratocarcinoma. The secretion of the plasminogen activator that accompanies this differentiation is an index of the biological response of F9 cells to these compounds. It is also known that the ability of these compounds to induce the plasminogen activator is directly correlated with the affinity and the activity they have on the RAR receptors endogenous to F9 cells.

(Skin Pharmacol., 1990, 3, pages 256-267). Among the agonist molecules of RARs that induce the differentiation of F9 cells, they can be more particularly cited; - the all-trans retinoic acid, - 2- (5,6,7,8-tetrahydro-5, 5, 8, 8-tetramethyl-2-naphthyl) -6-benzo [b] thiophene carboxylic acid, - the 4- [(5, 6, 7, 8-tetrahydro-5, 5, 8, 8-tetramethyl-2-naphthyl) carboxamido] benzoic acid, - 4- [5, 6, 7, 8-tetrahydro-5] , 5, 8, 8-tetramethyl-2-naphthyl) carbamoyl] benzoic acid. The sufficient amount of an agonist molecule of the RARs to be applied corresponds to that in which a response of the treated part of the skin of the mammal is observed after step (i). Thus, preferably and according to the nature of the agonist molecule of the RARs used, this amount varies between 0.0001% and 2% by weight per volume of applied solution. In the following or the foregoing, it is understood by topical route, any technique of administration of a product by direct application of the latter on a surface (or external) part of the body, and systemically, any technique of administration of a product. product by a route other than topical, for example enteral and / or parenteral. In the case of the systemic route, it is preferred to use the oral route. Retinoic acid antagonists are particularly the compounds described in EP 661,259, EP 740,937, EP 658,553, EP 568,898, WO 95/33745, WO 97/09297 and WO 94/14777, and in several scientific publications, mainly BYROLLES & cabbage. (J. Med. Chem., 37, 1994, 1508-1517, Med. Chem. Res., 2, 1992, 361-367.) And KANEKO &Cole. (Med. Chem. Res., 1, 1991). , 220-225) indicated here by way of reference and which inhibit the action of retinoic acid and / or retinoids The RAR antagonists useful according to the invention are in particular selected from the following compounds: - acid 4- f 7- ( 1-adamantyl) -6-methoxyethoxymethoxy-2-naphthyl] benzoic acid, 4- [7- (1-adamantyl) -6-methoxyethoxymethoxy-2-naphthyl] -salicylic acid, 6- [7- (1-adamantyl)] -6-methoxyethoxymethoxy-2-naphthyl] nicotinic acid, 4- {[5,6-dihydro-5,5-dimethyl-8- (4-methylphenyl) -2-n-phthalenyl] ethynyl} benzoic acid; (E) -4- [2- (4,4-dimethyl-7-heptyloxy-1,1-dioxo-3,4-dihydro-2H-1-benzothiopyran-6-yl) propenyl] benzoic acid, 4- [ 4, 5, 7, 8, 9, 10-hexahydro-7, 7, 10, 10-tetramethyl-1- (3-pyridylmethyl) anthra [1,2-b] pyrrol-3-yl] benzoic acid - - [4, 5, 7, 8, 9, 10-hexahydro-7, 7, 10, 10-tetramethyl-1- (3-pyridylmet il) thioanthra [1,2-b] pyrrol-3-yl] benzoic acid, 4- [4, 5, 7, 8,, 10-hexahydro-7, 7, 10, 10-tetramethyl-1- (3- pyridylmethyl) anthra [1,2-d] pyrazol-3-yl] benzoic acid, 4- [3-diadamantyl) -4-methoxybenzamido] benzoic acid, 4- [3-diadamantyl) -4-methoxybenzoyloxy] benzoic acid, - 4- (N-Phenyl-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphtho [2,3-d] imidazol-2-yl) benzoic acid - 4- (N-benzyl) acid -5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphtho [2,3-d] imidazol-2-yl) benzoic acid 4- (5H-7, 8, 9, 10- tetrahydro-5,7, 7, 10, 10-pentamethylbenzo [c] -naphtho [2, 3-b] [1,4] diazepin-3-yl) benzoic acid, 4- [1- (1-methoxy) 2,, 2-trifluoroethyl) -5, 6,7, 8-tetrahydro-5, 5, 8, 8-tetramethyl-3-anthracenyl] benzoic acid - 4- (5,5-dimethyl-8-phenyl-5,6-dihydro-naphthalene-2- iletinyl) enzoic, 4- (5,5-dimethyl-8-p-tolyl-5,6-dihydro-naphthalen-2-ylethynyl) benzoic acid, 4- [4-biphenyl-2-yl] but-3 acid -in-l-inyl) benzoic acid, (E) -4- [[3-oxo-3- [3- (1-adamantyl) -4-methoxyethoxymethoxyphenyl] -1-propenyl]] benzoic acid. The RARS antagonists useful according to the invention are preferably selected from the following compounds: 4- (5,5-dimethyl-8-p-tolyl-5,6-dihydro-naphthalen-2-ylethynyl) -benzoic acid - [7- (1-adamantyl) -6-methoxyethoxymethoxy-2-naphthyl] benzoic acid, 4- [7- (1-adamantyl) -6-methoxyethoxymethoxy-2-naphthyl] -salicylic acid - 6- [7- ( 1-adamantyl) -6-methoxyethoxymethoxy-2-naphthyl] nicotinic acid. Even more preferably, the antagonists RARs useful according to the invention are selected from the following compounds: 4- [7- (1-adamantyl) -6-methoxyethoxymethoxy-2-naphthyl] -salicylic acid, 6- [7- (1-adamantyl) -6- acid) ethoxyethoxymethoxy-2-naphthyl] nicotinic acid. Other characteristics, aspects, objects and advantages of the invention will appear even more clearly with the reading of the following description, as well as by the various concrete examples, but in no way restrictive, intended to illustrate it. It can be seen in a general way that, within the framework of the present invention, it is clearly completely possible to use mixtures of inhibitors, provided that these mixtures are understood to be compatible with the desired effect. The amount of inhibitor that can be used according to the invention is well understood depending on the effect sought. It also depends on the inhibitor. Therefore, it can vary within a broad limit. To provide an order of magnitude, if an inhibitor of retinoic acid activity is used in a cosmetic composition, it may contain the inhibitor in an amount representing from 0,0001% to 5% of the total weight of the composition and preferably in an amount representing from 0.01% to 2% of the total weight of the composition. To provide an order of magnitude, if an inhibitor of retinoic acid activity is used for the preparation of a dermatological composition, it can contain the inhibitor in an amount representing 0.001% to 15% of the total weight of the composition and preferably in an amount representing 0.1% to 10% of the total weight of the composition. In a general manner, it will be appreciated that all the products indicated above can be conventionally packaged in a manner appropriate to the mode of administration or application used for the latter (lotions, shampoos, tablets, syrups, nutritional supplements and others). The compositions can be classically conditioned in a manner convenient to the different modes of administration or application considered (lotions, shampoos, tablets, syrups and others).

Thus, the compositions are preferably conditioned in a convenient form for topical application. The compositions according to the invention can also resort to various conventional and customary additives, in particular cosmetics in the case of topical applications (capillary products in particular), chosen for example between UV filters, thickening agents, penetrating agents such as urea, organic solvents such as ethanol, isopropanol, alkylene glycols, surfactants, selected from nonionic surfactants such as alkyl polyglycosides, cationic surfactants, anionic surfactants and amphoteric surfactants, colorants, anti-peel agents, perfumes and preservatives. Of course, the compounds added to the compositions are chosen in such a way by the person skilled in the art that they do not counteract the desired effect of the present invention. It is also possible to integrate into the compositions of products already known as presenting an activity in the field of delay and / or inhibition of the growth of hairs and / or hairs. In this regard, mention may be made, for example, of cyclooxygenase inhibitors and / or lipoxygenase activators, such as those cited in patent applications EP-A-94/402055, WO-A-94/27586 or WO-A- 94/27563. In the same way, it is possible to integrate into the compositions products already known as presenters of an activity in the field of falling hair and / or hair and / or products that have an activity in the treatment of alopecia . Whatever the composition considered, it is possible to join in a single composition the inhibitor of the activity of the retinoic acid and the one or the other active components on the growth of the hairs and / or of the hair. But particular forms of realization can be considered, in particular the inhibitor of the activity of the retinoic acid and the other active component (s) can be administered simultaneously, separately or prolonged in time. Thus, the invention relates to a product comprising at least one inhibitor of the activity of retinoic acid and at least one other active component as a combination product for simultaneous, separate or prolonged use in order to delay and / or inhibit growth of the hairs and / or of the hair. Another object of the invention is a product comprising at least one inhibitor of the activity of retinoic acid and at least one other active component as a combination product for simultaneous, separate or stepwise use to delay the fall of hairs and / or hair hair In a particular embodiment, the inhibitor of the activity of the retinoic acid and the other active component (s) can be conditioned separately in the form of a kit from which the components will mix extemporaneously. The subject of the invention is therefore a kit comprising at least one retinoic acid activity inhibitor and at least one other active component for simultaneous, separate or prolonged use in order to delay and / or inhibit the growth of hairs and / or of the hair. The invention also relates to a kit comprising at least one inhibitor of the activity of the retinoic acid and at least one other active component for simultaneous, separate or stepwise use to delay the fall of the hairs and / or of the hair.

According to the invention, the inhibitor of the retinoic acid activity can be used in an amount ranging between 0.0001% and 15% by weight, preferably between 0.01% and 10%. Similarly, the cyclooxygenase inhibitor or the lipoxygenase activator can be used in an amount ranging between 0.001% and 5% by weight and preferably between 0.01% and 0.1% . According to yet another aspect of the present invention, a non-therapeutic treatment method for delaying or preventing the growth of hairs and / or hairs comprising administration to the organism, topically and / or systemically, has also been proposed. less an inhibitor of the activity of the retinoic acid, at doses such as those defined above, the organism being preferably a human being. According to yet another aspect of the present invention, a non-therapeutic treatment method has also been proposed for delaying the fall of the hairs and / or hairs comprising the administration to the organism, topically and / or systemically, of at least an inhibitor of the activity of the retinoic acid, at doses as defined above, the organism being preferably a human being. Preferably, the inhibitor of the retinoic acid activity is administered topically. According to a particularly preferred embodiment of the method according to the invention, compositions such as those defined above are applied to the skin and / or the scalp. To obtain remarkable effects, the frequency of administration or application of the compositions according to the invention is of the order of one to two times per day. In this regard, it has been found that sufficient amounts of inhibitory agents to be used in the context of the invention can generally remain very small. The present invention finds particularly useful applications in the field of treatments of the various pathologies that affect the pilosebaceous units of the skin and / or the scalp, in particular hirsutism. Concrete examples illustrating the invention will be given below. In all that follows or the foregoing, the percentages given are by weight, unless otherwise mentioned.

Example 1 : C57BL6 mice, male with an age of 42 days were selected for their hair cycle in the resting phase (telogen phase). They were shaved then (JO). The synthesis of melanin to intervene only on hairs in active phase, the skin of shaved mice is pink. The animals were divided into two groups, one receiving a composition comprising an inhibitor of the activity of the retinoic acid and the other being treated with the vehicle of this composition. 50 μl of these compositions were applied daily from Jl on a shaved surface (3 c) of the skin at concentrations varying from 0.1 to 0.3% of the inhibitor of retinoic acid activity. The animals were observed daily and the criteria corresponding to the surface thus treated were written down daily. The criteria are the following: Criterion 0: uniformly pink skin Criterion 1: appearance of a gray discoloration on the shaved surface Criterion 2: appearance of the first hair stems on the shaved surface Criterion 3: gray color on the whole of the shaved surface Criterion 4: presence of hairs on the whole of the shaved surface Criterion 5: hair born not different from the hair that has remained.

The results are given in the following tables: These results correspond to the area under the curve corresponding to the evolution of each criterion as a function of time (maximum observation duration: 90 days).

Table 1 Table 2 C itemes CD2665 CD2665 CD282? Come i u 1 or I (0.1%) (0.3%) (0.1%) and ÜÍJÜ y4 U¿J «UU5 8500 9105 y? ü 7555 8260 8880 8720 4335 5200 6465 5485 Table 3 CD2665 represents 4- [7- (1-adamantyl) -6-methoxyethoxy-methoxy-2-naphthyl] benzoic acid, CD2822 represents 6- [7- (1-adamantyl) -6-methoxyethoxy-methoxy-2-naphthyl] nicotinic acid, CD3106 represents 4- (5,5-dimethyl-8-p-tolyl-5,6 acid - dihydro-naphthalene-2-ylethynyl) benzoic acid, 9 CD2848 represents 4- [7- (1-adamantii) -6-methoxyethoxy-methoxy-2-naphthyl] -salicylic acid. The resumption of hair growth and lengthening are significantly delayed in animals that have been treated with an inhibitor of retinal acid activity as compared to animal is treated with the vehicle.

Example 2: Examples of formulations illustrating the invention. These compositions are obtained by simple mixing of the different components.

Composition 1: Lotion without rinse 4- [7- (1-adamantyl) -6-methoxyethoxy-methoxy-2-naphthyl] benzoic acid 1.0 g Propylene glycol 22.8 g Ethanol 95 ° 55.1 g Purified water csp 100 g Composition 2: Lotion with acid rinse 4- [7 (1-adamantyl) -6-mer.oxier.oxi-metsxy-2-naphthyl] salicylic 5.0 g Propylene glycol 22.8 g Absolute ethanol csp 100 g Composition 3: Lotion without rinsing Acid 4 - (5, 5-dimethyl-8-p-tolyl-5,6-dihydro-naphthalen-2-ylethynyl) enzoic 8.0 g Ethanol 95 ° 55.1 g Purified water csp 100 g It is noted that in relation to this date, the best method known by the applicant to carry out the aforementioned invention, is the conventional one for the manufacture of the objects or products to which it refers.

Claims (12)

1. Having described the invention as above, the content of the following claims is claimed as property: 1. Use in or for the preparation of a cosmetic or pharmaceutical composition, preferably dermatological, intended to delay and / or prevent the growth of hairs and / o of the hair, at least one inhibitor of the activity of the retinoic acid.
2. 2. Use in or for the preparation of a cosmetic or pharmaceutical composition, preferably dermatological, intended to delay the fall of the hair and / or the hair, of at least one inhibitor of the activity of the retinoic acid.
3. 3. Use according to the preceding claim, characterized in that the inhibitor of retinoic acid activity is administered topically or systemically.
4. 4. Utilization of coryxity with the preceding claim, characterized in that the inhibitor of the activity of the retinoic acid is administered topically.
5. 5. Use according to any of the preceding claims, characterized in that the inhibitor of the activity of retinoic acid is chosen from: 4- [7- (1-adamantii) -6-methoxyethoxymethoxy-2-naphthyl] benzoic acid, 4- [7- (1-adamantyl) -6-methoxyethoxymethoxy-2-naphthyl] salicyclic acid, 6- [7- (1-adamantyl) -6-methoxyethoxymethoxy-2-naphthyl] nicotinic acid, 4- acid. { [5,6-dihydro-5,5-dimethyl-8- (4-methylphenia) -2-naphthalene] ethynybenzoic acid, (E) -4- [2- (4,4-dimethyl-7-heptyloxy-1) acid, 1-dioxo-3, -dihydro-2H-1-benzothiopyran-6-yl) propeni1] benzoic acid, 4- [4, 5, 7, 8, 9, I0-hexahydro-7, 7, 10, 10-tetramethyl] -l- (3-pyridylmethyl) anthra [1,2-b] pyrrol-3-yl] benzoic acid, 4- [4, 5, 7, 8, 9, 10-hexahydro-7, 7, 10, 10- tetramethi-1- (3-pyridylmethyl) thioanthra [1, 2-bjpyrid-Sil] benzoic acid, 4- [4, 5, 7, 8, 9, 10-hexahydro-7, 7, 10, 10-tetramethi-1] - (3-pyridiimetii) anthra [1,2-d] pyrazol-3-yl] benzoic acid - 4- [3-diadamanthyl) -4-methoxybenzamido] benzoic acid, - 4- [3-diadamantii] -4- methoxybenzoyl i] benzoic acid - 4- (N-phenyl-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphtho [2,3-d] imidazol-2-yl) benzoic acid - acid 4- (N-benzyi-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphtho [2,3-d] imidazol-2-yl) benzoic acid - 4- (5H-7, 8, 9, 10-tetrahydro-5,7,7,10,10-pentamethylbenzo [c] -naphtho [2,3-b] [1,4] diazepin-3-yl) benzoic, - 4- [1- (l-methoxy-2,2,2-trifluoroethyl) -5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-3-anthracenyl] benzoic acid 4- (5, 5-metii-8-phene-5,6-dihydxonaphthalen-2-ylethynyl) benzoic acid - 4- (5,5-dimethyl-8-p-tolyl-5,6-dihydronaphthalene-2- iletinyl) benzoic acid, 4- [4-bipheni-2-yl) but-3-en-l-ynyl) benzoic acid, (E) -4- [[S-oxo-3- [3- (1-adamantii]] ) -4-methoxyethoxymethoxyphenyl] -1-propenyl]] benzoic acid.
6. 6. Use in a cosmetic composition according to any of the preceding claims, characterized in that the inhibitor of the activity of retinoic acid is in a concentration ranging between 0, 0001% and 5% and preferably between 0.01% and 2% by weight relative to the total weight of the composition.
7. 7. Use for the preparation of a dermatological composition according to any of claims 1 to 5, characterized in that the inhibitor of the activity of retinoic acid is in a concentration ranging between 0.001% and 15% and preferably between 0 , 1% and 10% by weight in relation to the total weight of the composition.
8. 8. Non-therapeutic treatment method for delaying or preventing the growth of the hairs, comprising the administration to the body, topically and / or systemically, of at least one inhibitor of the activity of the retinoic acid as defined in claims 1 and 3 to 6.
9. 9. Non-therapeutic treatment method for delaying the fall of hairs and / or hairs comprising the administration to the organism, topically and / or systemically, of at least one inhibitor of the activity of retinoic acid as defined in claims 2 to 6.
10. 10. Product, characterized in that it comprises at least one inhibitor of the activity of the retinoic acid and at least one other active component for simultaneous, separate or stepwise use to delay and / or inhibit the growth of the hairs and / or of the hair.
11. 11. A characterized product comprises at least one inhibitor of the activity of the retinoic acid and at least one other active component for simultaneous, separate or stepwise use to delay the fall of the hairs and / or of the hair.
12. 12. Product according to any of claims 10 and 11, characterized in that it is presented in the form of a kit.