RU2193877C2 - Agent for changing hair growth in cosmetic or pharmaceutical composition, method for nontherapeutic treatment of hair and kit - Google Patents

Abstract

FIELD: cosmetology, pharmaceutics, dermatology. SUBSTANCE: innovation deals with application of an agent in cosmetic, pharmaceutical, preferably dermatological composition or with obtaining, at least, one inhibitor of retinoic acid activity. Moreover, said composition is indicated to deteriorate or prevent hair growth. It is, also, indicated to deteriorate hair fall-out. The innovation deals with the method to treat hair including either local or systemic inhibitor of retinoic acid activity and with a kit including an inhibitor of retinoic acid activity and another active component. EFFECT: higher efficiency of hair care. 15 cl, 2 ex, 3 tbl

Description

 The invention relates, in its most general form, to use in a cosmetic composition or to obtain a pharmaceutical composition for inhibiting or preventing hair growth of at least one retinoic acid activity inhibitor. The compositions of the present invention are also intended to delay hair loss. It also relates to a non-therapeutic treatment method for altering hair growth.

 In humans, hair growth and renewal are determined mainly by the activity of hair follicles. Their activity is cyclic and includes essentially three phases, namely the anagenic phase, the catagenic phase and the telogenic phase.

 The active anagen phase, or the growth phase, which lasts several years and during which the hair is lengthened, is followed by a very short and transitional catagen phase, which lasts several weeks, then it is replaced by the resting phase, called the telogenic phase, which lasts several months.

 At the end of the rest period, the hair falls out and a new cycle begins. Consequently, the hair is constantly renewed and for about 150,000 hairs forming a head of hair, at each moment about 10% of them are at rest and, therefore, will be replaced within a few months.

 In a significant number of cases, in genetically predisposed subjects, premature hair loss occurs, and it is especially common in men. It is mainly about androgenetic or androgenic or even androgen-genetic alopecia.

 This alopecia essentially occurs due to perturbation of the hair renewal, which causes, firstly, an increase in the frequency of the repetition of cycles due to the quality of the hair, then their quantity. There is a gradual depletion of hair due to the regression of the so-called "terminal" hair in the gun stage. Mostly, the areas of the temporal or frontal bulbs in men are affected, and in women there is diffuse alopecia of the crown.

 For many years, in the cosmetic and pharmaceutical industries, research has been carried out in the direction of finding substances that can eliminate or reduce the effect of baldness and, in particular, reduce hair loss or cause or stimulate their growth.

 In this regard, of course, a large number of very different active substances or compounds have already been proposed. Among other things, for information, vitamins, such as vitamin E, amino acids, such as, for example, serine or methionine, vasodilators, such as acetylcholine and its derivatives, estrogen hormones, such as estradiol, keratolytic agents, such as salicylic acid, or chemical compounds such as, for example, 2,4-diamino-6-piperidinopyrimidin-3-oxide or minoxidil described in US Pat. No. 4,596,812, or its numerous derivatives, as described, for example, in European patent applications. 353123, 356271, 408442, 522964, 420707, 459890, 519 819. You can also name 6-amino-1,2-dihydro-1-hydroxy-2-imino-4-piperidinopyrimidine and its derivatives, which are described mainly in application for US patent 4139619.

 However, there remains an interest in other active substances that differ from the known ones.

 Minoxidil, which is a standard (reference) compound in this area, has pronounced side effects, which make it necessary to be careful with its use.

 Identification of substances that affect the growth and / or hair loss without negative side effects remains the main object of search.

 In addition, it is of interest to identify compounds that can slow hair growth.

 In general, it is known that retinoic acid, which is fully in transconfiguration, acts on the differentiation and / or proliferation of cells by interacting with the nuclear receptors or RARs (retinoic acid receptors) contained in the cell nucleus. Numerous synthetic structural analogues of retinoic acid, which is fully in the trans configuration, or 9-cis-retinoic acid, briefly called "retinoids", are currently described in the literature. There are currently three identified subtypes of RAR receptors, called α-RAR, β-RAR, and γ-RAR, respectively. These receptors, after ligand fixation (that is, completely in the transconfiguration of 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 subtype of a single RAR receptor (α, β or γ). Other analogues, finally, do not have any individual selective activity in relation to these various receptors. In this regard, for example, the retinoic acid, which is fully in the transconfiguration, activates all subtypes of RARs combined (specific for the ligand of the agonist RARs).

 Retinoic acid and, in general, retinoids, by binding to RARs receptors, which allows the regulation of RARs receptor activity, are described as capable of treating numerous skin disorders or diseases, and in particular baldness.

 Retinoic acid antagonists, in contrast, can inhibit the activity of retinoic acid or its metabolites at the cellular level. This is mainly about RARs antagonists that can bind to RARs but do not stimulate the activity observed for retinoic acid or retinoids.

 Thus, it has been shown that α-RAR receptor antagonists inhibit cell differentiation induced by retinoids in HL60 cell line cells, or, conversely, reverse the inhibition of mouse B cell proliferation induced by retinoids (C. Apfel et al., Proc. Natl. Acad. Sci. USA 89, 7129-7133 [1992]).

 Various retinoic acid antagonists are described in European patent application 0740937. They are recommended for the treatment of disorders and / or diseases associated with hyperregulation of RARs and / or hypervitaminosis A, most often expressed as an inflammatory, allergic and / or immunological component, such as psoriasis. They are also described as treating baldness.

 So, after significant studies, the applicant has now found that by inhibiting the activity of retinoic acid in skin cells in the vicinity of hair follicles, it is possible to significantly slow down the hair development cycle, and especially the anagenic phase or telogenic phase.

 Even more specifically, it has been found that by inhibiting the activity of retinoic acid, it is possible to slow down and / or prevent hair growth and / or delay hair loss.

 This discovery forms the basis of the present invention.

 Thus, according to a first aspect of the present invention, there is provided the use, in a cosmetic or pharmaceutical, preferably dermatological, composition, or for its preparation, for inhibiting and / or preventing hair growth of at least one retinoic acid activity inhibitor.

 According to a second aspect of the invention, there is provided the use, in a cosmetic or pharmaceutical, preferably dermatological, composition, or for its preparation, for delaying hair loss of at least one retinoic acid activity inhibitor.

 Inhibitors of the activity of retinoic acid can act in two ways, of which the first is to accelerate the cellular metabolism of retinoic acid to reduce its concentration in cells, the second - to counteract its action at the cellular level.

 Therefore, retinoic acid activity inhibitors according to the invention can be retinoic acid metabolism accelerators or antagonists, inverse agonists or partial retinoic acid agonists.

 By retinoic acid antagonists, preferably, according to the invention, are meant compounds that inhibit the effects of retinoic acid and / or its metabolites and / or retinoids. More specifically, we are talking about RARs antagonists that are fixed on RARs receptors, however, without their activation.

In particular, compounds that inhibit the activity of retinoic acid "in vivo", selected according to the test described in the application for European patent 96401170, filed May 31, 1996 in the name of CIRD GALDERMA. This is a method for identifying RARs antagonist molecules, which is characterized in that it comprises the following steps: (i) a sufficient number of RARs agonist molecules are locally applied to a portion of the skin of a mammal, (ii) by a systemic or local route to the same mammal or to the same a portion of the skin of the mammal, before, during or after step (i), molecules capable of antagonizing RARs are administered, and (iii) the response to the thus treated portion of the skin of the mammal is evaluated. Thus, when the introduced molecules are an antagonist of RARs, an increase in the thickness of the treated portion of the skin of the mammal under the action of RARs agonist molecules is not detected or appears to a weakened extent. Therefore, inhibition of the response is observed. In practice, the mammal is a rodent, such as a mouse, rat, guinea pig, hamster or rabbit. The used portion of the skin of a mammal may be any part of the body of a mammal. The estimated response to the thus treated part of the skin of a mammal corresponds to its clinical change. Typically, this evaluated response corresponds to a change in the thickness of the thus treated portion of the skin. The thickness measurement of the thus treated part of the skin can be carried out in any known manner. When the used part of the skin is smooth, you can measure its thickness by bending it. In practice, use the skin of the ear. Ear thickness measurement can be done with the oditest micrometer. Of course, the assessment in step (iii) corresponds to determining the response of the thus treated part of the skin and comparing the results of this determination with the response values of the same part of the skin treated under the same conditions only with RARs agonist molecules. RARs agonist molecules are preferably selected among compounds capable of inducing cell differentiation (F9) of mouse embryonic teratocarcinoma. The secretion of plasminogen activator, which accompanies this differentiation, is an indicator of the biological response of F9 cells to these compounds. It is also known that the ability of these compounds to stimulate plasminogen activator directly correlates with the affinity and activity that they have for endogenous RARs receptors in F9 cells (Skin Pharmacol., 3, 256-267 [1990]). Of the RARs agonist molecules that stimulate the differentiation of F9 cells, in particular we can name:
retinoic acid, which is fully in the trans configuration,
- 2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -6-benzo [b] thiophenecarboxylic acid,
- 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.

 A sufficient amount of RARs agonist molecules to be applied corresponds to the amount at which a response of the treated portion of the skin of the mammal is observed after step (i). Thus, it is preferable and depending on the nature of the RARs agonist molecules used, this amount is from 0.0001 wt.% To 2 wt.% Per volume of the solution to be applied.

 In the following or in the above text of the present application, the local route is understood to mean any method of product administration by direct application of the latter to the external (or external) part of the body, and the systemic path is understood to mean any method of product administration by a route other than the local, for example, enteral and / or parenteral by way. In the case of the systemic route, an oral route of administration is preferred.

 Retinoic acid antagonists are, in particular, the compounds described in European patent applications 661259, 740937, 658553, 568898; in international patent applications 95/33745, 97/09297 and 94/14777; and in several scientific publications, in particular Eyrolles et al. (J. Med. Chem., 37, 1508-1517 [1994]; Med. Chem. Res. 2, 361-367 [1992]) and Kaneko et al. . (Med. Chem. Res., 1, 220-225 [1991]), incorporated herein by reference, which inhibit the effects of retinoic acid and / or retinoids.

Suitable RARs antagonists according to the invention are in particular selected from the following compounds:
-4- [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-naphthalenyl] 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- [4,5,7,8,9,9-hexahydro-7,7,10,10-tetramethyl-1- (3-pyridylmethyl) anthra [1,2-b] pyrrol-3-yl] benzoic acid;
-4- [4,5,7,8,9,9-hexahydro-7,7,10,10-tetramethyl-1 (3-pyridylmethyl) thioanthra [1,2-b] pyrrol-3-yl] benzoic acid;
-4- [4,5,7,8,9,9-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-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-2,2,2-trifluoroethyl) -5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-3-anthracenyl] benzoic acid;
-4- (5,5-dimethyl-8-phenyl-5,6-dihydronaphthalen-2-ylethinyl) benzoic acid;
-4- (5,5-dimethyl-8-p-tolyl-5,6-dihydronaphthalen-2-ylethinyl) benzoic acid;
-4- [4- (diphenyl-2-yl) but-3-en-1-ynyl) benzoic acid;
- (E) -4- [3-oxo-3- [3- (1-adamantyl) -4-methoxyethoxymethoxyphenyl] -1-propenyl] benzoic acid.

Suitable RARs antagonists of the invention are preferably selected from the following compounds:
-4- (5,5-dimethyl-8-p-tolyl-5,6-dihydronaphthalen-2-ylethinyl) benzoic acid;
-4- [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, RARs antagonists 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-methoxyethoxymethoxy-2-naphthyl] nicotinic acid.

 Other characteristics, aspects, objects and advantages of the invention will become even clearer after reading the following description, as well as various specific examples, intended to illustrate, but in no way limiting the scope of protection of the invention.

 In General, you can notice that in the framework of the present invention, of course, you can use a mixture of inhibitors, of course, provided that only these mixtures remain compatible with the desired effect.

 The amount of inhibitor that can be used according to the invention, of course, depends on the desired effect. It also depends on the inhibitor. Therefore, it can vary within wide limits.

 With respect to indicating order of magnitude, if an inhibitor of retinoic acid activity is used in a cosmetic composition, it may contain an inhibitor in an amount of from 0.0001 wt.% To 5 wt.% With respect to the total weight of the composition and preferably in an amount of 0.01-2 wt. % relative to the total weight of the composition.

 With respect to indicating order of magnitude, if a retinoic acid activity inhibitor is used to produce a dermatological composition, it may contain an inhibitor in an amount of from 0.001 wt.% To 15 wt.%, Relative to the total weight of the composition, and preferably in an amount of 0.1-10 wt. %, relative to the total weight of the composition.

 In general, it should be noted that all of the above products can usually be in a form suitable for the chosen method of administration or application of the latter (lotions, shampoos, tablets, syrups, food additives and others).

 The compositions can usually be in a form suitable for the various contemplated routes of administration or application (lotions, shampoos, tablets, syrups and others). Thus, the compositions are preferably in a form suitable for topical application.

 Compositions according to the invention can also contain various classic and conventional, especially cosmetic, additives, in the case of local applications (in particular, hair products), selected, for example, from ultraviolet filters, thickeners, facilitating the penetration of components such as urea, organic solvents such as ethanol, isopropanol, alkylene glycols, surfactants selected from nonionic surfactants such as alkyl polyglycosides, cationic surfactants spot-active substances, anionic surfactants and amphoteric surfactants, dyes, antidandruff ingredients, fragrances and preservatives.

 Of course, the specialist selects the compounds added to the compositions in such a way that they do not impair the desired effect of the present invention.

 Products that are already known to have activity in the field of inhibiting and / or inhibiting hair growth may also be included in the composition.

 In this regard, mention may be made, for example, of cyclooxygenase inhibitors and / or lipoxygenase activators, as indicated in European Patent Application A-94/402055, International Patent Applications A-94/27586 and A-94/27563.

 Products that are already known to be active in the field of hair loss and / or products that are active in the treatment of baldness can be introduced into the composition in the same way.

 Whatever the composition envisaged, a retinoic acid activity inhibitor and other or other hair growth active components may be combined in one composition. However, specific forms of implementation may be provided, in particular an inhibitor of the activity of retinoic acid and other or other active components can be administered simultaneously, separately or distributed in time.

 Thus, the subject of the invention is a product comprising at least one retinoic acid activity inhibitor and at least one other active component, as a combined product for simultaneous, separate or time-distributed use in order to slow and / or inhibit hair growth.

 The subject of the invention is also a product comprising at least one retinoic acid activity inhibitor and at least one other active component as a combined product for simultaneous, separate or time-distributed use in order to delay hair loss.

 According to a particular embodiment, the retinoic acid activity inhibitor and the other or other active components may be packaged separately as a kit, the components of which are mixed at the time of use.

 Thus, the subject of the invention is a kit containing at least one retinoic acid activity inhibitor and at least one other active component, for simultaneous, separate or time-distributed use in order to slow and / or inhibit hair growth.

 The invention also relates to a kit containing at least one retinoic acid activity inhibitor and at least one other active component, for simultaneous, separate or time-distributed use in order to delay deposition.

 According to the invention, the retinoic acid activity inhibitor can be used in an amount of 0.0001-15 wt.%, Preferably 0.01-10 wt.%.

 Similarly, a cyclooxygenase inhibitor or lipoxygenase activator can be used in an amount of 0.001-5 wt.% And preferably 0.01-0.1 wt. %

 According to another aspect of the present invention, there is also provided a non-therapeutic treatment method for slowing down or preventing hair growth, which comprises the local and / or systemic administration of at least one retinoic acid activity inhibitor in doses such as those mentioned above, the body being preferably the human body .

 According to yet another aspect of the present invention, there is also provided a non-therapeutic treatment method for delaying hair loss, which comprises the local and / or systemic administration of at least one retinoic acid activity inhibitor in doses such as those indicated above, the body being preferably the human body.

 The retinoic acid activity inhibitor is preferably administered locally.

 According to a particularly preferred embodiment of the method according to the invention, compositions such as those mentioned above are applied to the skin and / or to the skin of the scalp.

 To achieve significant effects, the frequency of administration or application of the compositions of the invention is on the order of one to two times a day. In this regard, it should be noted that a sufficient number of inhibitors used in the framework of the invention are generally very small.

 The present invention finds application, in particular in the field of treatment of various pathologies affecting the sebaceous hair units of the skin and / or skin of the scalp, in particular hirsutism.

 The following are specific examples illustrating the invention. In the following or in the above text of the application, the percentage data refers to the mass, unless otherwise indicated.

Example 1
Male C57BL6 mice at the age of 42 days were selected according to their hair development cycle in the resting phase (telogenic phase). Then they were shaved (day 0). Since melanin synthesis occurs only in hair in the active phase, the skin of shaved mice is pink.

 The animals were divided into two groups, of which one received a composition containing a retinoic acid activity inhibitor, and the other was treated with an excipient of this composition.

50 μl of these compositions daily, starting from day 1, was applied to the shaved surface (3 cm ² ) of the skin in concentrations ranging from 0.1 to 0.3% retinoic acid activity inhibitor.

Animals were observed daily and criteria corresponding to the surface thus treated were noted daily. The criteria were as follows:
criterion 0: equally pink skin,
criterion 1: the appearance of gray staining in the form of spots on a shaved surface,
criterion 2: the appearance of the first hair rods on a shaved surface,
criterion 3: gray color on the entire shaved surface,
criterion 4: the presence of hairs on the entire shaved surface,
criterion 5: regrowth hairs not different from the remaining hair.

 The results are presented in table. 1-3. 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).

In Table 1-3, CD2665 means 4- [7- (1-adamantyl) -6-methoxyethoxymethoxy-2-naphthyl] benzoic acid;
CD2822 is 6- [7- (1-adamantyl) -6-methoxyethoxymethoxy-2-naphthyl] nicotinic acid;
CD3106 means 4- (5,5-dimethyl-8-p-tolyl-5,6-dihydronaphthalen-2-ylethynyl) benzoic acid;
CD2848 means 4- [7- (1-adamantyl) -6-methoxyethoxymethoxy-2-naphthyl] salicylic acid.

 Activation of growth and elongation of hairs were significantly slowed down in animals that were treated with an inhibitor of the activity of retinoic acid, compared with animals treated with an excipient.

Example 2
Examples of formulations illustrating the invention are provided. These compositions were prepared by simple mixing of various components.

Composition 1: indelible lotion
4- [7- (1-adamantyl) -6-methoxyethoxymethoxy-2-naphthyl] benzoic acid - 1.0 g
propylene glycol - 22.8 g
ethanol, 95 ^o - 55.1 g
purified water a sufficient amount up to - 100 g
Composition 2: Rinse off lotion
4- [7- (1-adamantyl) -6-methoxyethoxymethoxy-2-naphthyl] salicylic acid - 5.0 g
propylene glycol - 22.8 g
absolute ethanol a sufficient amount up to - 100 g
Composition 3: indelible lotion
4- (5,5-dimethyl-8-p-tolyl-5,6-dihydronaphthalen-2-yl-ethynyl) -benzoic acid - 8.0 g
ethanol, 95 ^o - 55.1 g
purified water a sufficient amount up to - 100 g

Claims (14)

 1. The use of at least one retinoic acid activity inhibitor as an agent for altering hair growth in a cosmetic or pharmaceutical composition, preferably a dermatological composition.  2. The use according to claim 1, characterized in that the composition is intended to slow and / or prevent hair growth.  3. The use according to claim 1, characterized in that the composition is intended to delay hair loss.  4. The use according to any one of paragraphs. 1-3, characterized in that the retinoic acid activity inhibitor is administered locally or systemically.  5. The use according to claim 4, characterized in that the retinoic acid activity inhibitor is administered locally. 6. The use according to any one of paragraphs. 1-5, characterized in that the retinoic acid activity inhibitor is selected from the group consisting of:
-4- [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-naphthalenyl] 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- [4,5,7,8,9,9-hexahydro-7,7,10,10-tetramethyl-1- (3-pyridylmethyl) anthra [1,2-b] pyrrol-3-yl] benzoic acid;
-4- [4,5,7,8,9,9-hexahydro-7,7,10,10-tetramethyl-1- (3-pyridylmethyl) thioanthra [1,2-b] pyrrol-3-yl] benzoic acid;
-4- [4,5,7,8,9,9-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-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 acids;
-4- [1- (1-methoxy-2,2,2-trifluoroethyl) -5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-3-anthracenyl] benzoic acid;
-4- (5,5-dimethyl-8-phenyl-5,6-dihydronaphthalen-2-ylethinyl) benzoic acid;
-4- (5,5-dimethyl-8-p-tolyl-5,6-dihydronaphthalen-2-ylethinyl) benzoic acid;
-4- [4- (diphenyl-2-yl) but-3-en-1-ynyl) benzoic acid;
- (E) -4- [3-oxo-3- [3- (1-adamantyl) -4-methoxyethoxymethoxyphenyl] -1-propenyl] benzoic acid.  7. The use in a cosmetic composition according to any one of paragraphs. 1-6, characterized in that the retinoic acid activity inhibitor is in a concentration of from 0.0001 to 5 wt. %, preferably 0.01-2 wt. %, relative to the total weight of the composition.  8. Application to obtain a dermatological composition according to any one of paragraphs. 1-6, characterized in that the retinoic acid activity inhibitor is in a concentration of from 0.001 to 15 wt. %, preferably 0.1-10 wt. %, relative to the total weight of the composition.  9. A method of non-therapeutic treatment of hair to change their growth, including the introduction into the body of the local and / or systemic route of at least one retinoic acid activity inhibitor, such as specified in paragraphs. 1 and 4-7.  10. The method according to p. 9, characterized in that it is used to slow down and / or prevent hair growth.  11. The method according to p. 9, characterized in that it is used to delay hair loss.  12. A kit comprising at least one retinoic acid activity inhibitor and at least one other active component for simultaneous, separate or time-distributed use in order to change hair growth.  13. The kit according to p. 12, characterized in that it is used to slow down and / or prevent hair growth.  14. The kit according to p. 12, characterized in that it is used to delay hair loss.

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