FR2846232A1 - Using styryl-pyrazole compounds for treating hair loss, stimulating hair growth or increasing hair density, and as inhibitors of 15-hydroxyprostaglandin dehydrogenase - Google Patents

Abstract

Use of at least one styryl-pyrazole compound (I), or its salt, (a) for inducing and/or stimulating growth of hair, inhibiting hair loss and/or increasing hair density or (b) as inhibitor of 15-hydroxyprostaglandin dehydrogenase (15-PGDH). Use of at least one styryl-pyrazole compound of formula (I), or its salt, (a) for inducing and/or stimulating growth of hair, inhibiting hair loss and/or increasing hair density or (b) as inhibitor of 15-hydroxyprostaglandin dehydrogenase (15-PGDH). R1, R2, R4 and R5 = hydrogen, halo, OR7, SR7, NR7R'7, COOR7, CONR7R'7, trifluoromethyl, cyano, NR7COR'7, SO2R7, SO2NR7R'7, NR7SO2R'7, COR7, CSR7, OCOR7, COSR7, SCOR7, CSNR7R'7, NR7CONR'7R''7, NR7C(=NR'7)NR''7R'''7, NR7CSR'7, NR7CSNR'7R''7, 1-20C alkyl (optionally unsaturated), 4-7 membered (un)saturated rings, optionally containing at least one heteroatom, either separated or fused, and alkyl groups and rings may be substituted by at least one A1; R7, R'7, R''7 and R'''7 = hydrogen, 1-20C alkyl or 4-7 atom ring, both optionally unsaturated and/or substituted by at least one A2; R3 = cyano, COOR8, CONR8R'8, COR8, SO2R8 or SO2NR8R'8; R8 and R'8 = hydrogen, 1-20C alkyl or 4-7 atom ring, both optionally unsaturated and/or substituted by at least one A3; R6 = hydrogen, COOR9, COR9, CSR9, COSR9, CONR9R'9, SO2R9, SO2NR9R'9, 1-20C alkyl (optionally unsaturated), 4-7 membered (un)saturated rings, optionally containing at least one heteroatom, either separated or fused, and alkyl groups and rings may be substituted by at least one A4; R9 and R'9 = hydrogen, 1-20C alkyl or 4-7 atom ring, both optionally unsaturated and/or substituted by at least one A5; A1-A5 = halo, OR10, SR10, NR10R'10, COOR10, CH2COOR10, CONR10R'10, trifluoroamethyl, cyano, NR10COR'10, SO2R10, SO2NR10R'10, NR10SO2R'10, COR10, CSR10, OCOR10, COSR10, SCOR10, CSNR10R'10, NR10CONR'10R''10, NR10(=NR'10)NR''10R'''10, NR10CSNR'10R''10 or NR10CSR'10; R10-R'''10 = hydrogen, 1-20C alkyl or 4-7 atom ring, optionally containing at least one heteroatom and either isolated or fused, both optionally unsaturated.

Description

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The subject of the invention is a hair care composition containing an effective amount of a pyrazole compound and more particularly a styryl-pyrazole, intended to induce and / or stimulate hair growth and / or to slow down their fall. It further relates to a cosmetic treatment method for stimulating hair growth and / or curbing hair loss.

Hair growth and renewal are mainly determined by the activity of hair follicles and their matrix environment. Their activity is cyclic and comprises essentially three phases, namely the anagen phase, the catagen phase and the telogen phase.

In the anagen phase (active or growth phase), which lasts several years and during which the hair lengthens, follows a very short and transient catagen phase that lasts a few weeks. During this phase, the hair undergoes an evolution, the follicle atrophies and its dermal implantation appears more and more high.

The terminal phase or telogen phase, which lasts a few months, corresponds to a rest phase of the follicle and the hair eventually falls. At the end of this rest period, a new follicle is regenerated, on the spot, and another cycle begins again.

The hair is therefore constantly renewed and about 150,000 hairs of hair, about 10% are at rest and will be replaced in a few months.

The fall or natural loss of hair can be estimated, on average, to a few hundred hairs a day for a normal physiological state. This process of permanent physical renewal undergoes a natural evolution during aging, the hair becomes thinner and their cycles shorter.

In addition, various causes can lead to a significant loss, temporary or permanent hair. It can be a fall and a deterioration of the hair at the end of a pregnancy (post partum), during states of malnutrition or imbalances of food or during states of asthenia or hormonal dysfunction as this may be the case during or after menopause. It can also be a fall or alterations of the hair in relation to seasonal phenomena.

It may also be alopecia, which is mainly due to a disruption of capillary renewal leading initially to the acceleration of the frequency of the cycles at the expense of the quality of the hair, then their quantity. Successive growth cycles lead to increasingly fine and shorter hair, gradually turning into an unpigmented down. Areas are affected preferentially, including the temporal or frontal gulfs in humans, and in women, there is diffuse alopecia of the vertex.

The term alopecia also covers a whole family of damage to the hair follicle, the final consequence of which is definitive, partial or general loss of hair. It is more particularly androgenic alopecia. In a large number of cases, the early fall of the hair occurs in subjects predisposed genetically, it is then andro-chrono-genetic alopecia; this form of alopecia concerns especially men.

It is known, moreover, that certain factors such as a hormonal imbalance, a physiological stress, the malnutrition, can accentuate the phenomenon.

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 In certain dermatoses of the scalp with an inflammatory characteristic, such as, for example, psoriasis or seborrheic dermatitis, the hair loss can be greatly accentuated or cause cycles of the highly disturbed follicles.

For many years, it has been sought in the cosmetic or pharmaceutical industry compositions that make it possible to eliminate or reduce alopecia, and in particular to induce or stimulate hair growth or to reduce hair loss.

In this regard, it has already been proposed a large number of compositions comprising a wide variety of active ingredients, such as for example 2,4-diamino 6-piperidinopyrimidine oxide or "minoxidil" described in US Pat. Nos. 4,139,619 and 4,596,812 or US Pat. still its numerous derivatives such as those described for example in the documents EP 0353123, EP 0356271, EP 0408442, EP 0522964, EP 0420707, EP 0459890, EP 0519819.

Clinical studies have demonstrated that PGF2-α analogs have the property of causing hair and eyelash growth in humans and animals (Murray A and Johnstone, MD, 1997. Am. J. Opht., 124 (4), 544-547). In humans, tests on the scalp have shown that an analogue of prostaglandin E2 (viprostol) has the property of increasing capillary density (Roenigk HH, 1988. Clinic Dermatol., 6 (4), 119 -121).

Furthermore, the patent WO 98/33497 describes pharmaceutical compositions containing prostaglandins or prostaglandin derivatives intended to combat hair loss in humans. Prostaglandins of type A2, F2a and E2 are mentioned as preferred.

However, prostaglandins are molecules with a very short half-life time and acting autocrine or paracrine, reflecting the local and labile nature of prostaglandin metabolism (Narumiya S. et al., 1999, Physiol. 79 (4), 1193-1226).

It therefore seems important, in order to maintain and / or increase the capillary density in humans, to preserve the endogenous reserves of PGF2-a and of PGE2 of the different compartments of the hair follicle or of its near skin environment. A solution giving good results is the use of lipoxygenase inhibiting compounds and / or cyclooxygenase inducers to promote hair growth; One hypothesis is that the use of such compounds directs the metabolism of fatty acids towards endogenous prostaglandin synthesis in preference to other pathways.

However, to further improve the results, it would be desirable to be able to prolong the activity of prostaglandins involved in the growth and maintenance of the hair alive.

différenciation tels que les kératines Ki et K10 ne sont pas exprimés dans le follicule pileux et en particulier dans la gaine externe (Lenoir et al., 1988, Dev. Biol. 130 610- 620), que la trichohyaline (O'Guin et al., 1992, J. Invest. Dermatol 98 . 24-32) et la It is also well known that the differentiation programs of the keratinocytes of the epidermis and the hair follicle are clearly different. Thus, it is known that the keratin of the hair shaft represents a family (Langbein et al., 2001, J Biol Chem 276: 35123-35132) distinct from that expressed in the epidermis, that the markers of

differentiation such as Ki and K10 keratins are not expressed in the hair follicle and in particular in the outer sheath (Lenoir et al., 1988, Dev Biol 130 610-620), that trichohyaline (O'Guin et al. 1992, J. Invest Dermatol 98, 24-32) and the

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 keratin keratin (Porter et al., 2001, Br J. Dermatol 145: 558-568) are expressed in the hair follicle especially in the inner sheath but not in the epidermis, and that cyclooxygenase type 1 if it is expressed in the epidermis, it is not in the keratinocytes of the hair follicle but in the dermal papilla (Michelet et al., 1997, J. Invest Dermatol 108: 205-209).

Surprisingly, the Applicant has now demonstrated that an enzyme specifically involved in the degradation of these prostaglandins is present in the dermal papilla of the hair, which is a critical compartment for the life of the hair. Indeed, the Applicant has now proved the presence of 15-hydroxy prostaglandin dehydrogenase (abbreviated 15-PGDH) at this level. It has further shown that inhibition of 15-PGDH has a beneficial effect on hair growth.

This is why the present invention relates to a care or hair treatment composition containing at least one particular inhibitor of 15-hydroxyprostaglandin dehydrogenase and a physiologically acceptable medium.

15-PGDH is a key enzyme in the deactivation of prostaglandins, particularly PGF2-a, and PGE2, which are important mediators of hair growth and survival. It meets the classification EC 1 1 1. 141 and is NAD + dependent. She was isolated from pork kidney; in particular, it has been observed to be inhibited by a thyroid hormone, tri-iodo thyronine, at doses much higher than the physiological doses.

However, it has never been proposed to use a 15-PGDH inhibitor to maintain and / or increase capillary density and / or to reduce the heterogeneity of human hair diameters. By increasing the capillary density, it is intended to increase the number of hair per cm 2 of scalp.

The Applicant has found that certain pyrazole compounds, and in particular certain salty or non-salified styryl-pyrazoles, are surprisingly provided with an activity that is favorable to the improvement of the capillary density. He further found that these compounds are inhibitors of 15-hydroxyprostaglandin dehydrogenase.

dans laquelle : - R1, R2, R4 et R5 identiques ou différents sont choisis parmi l'hydrogène, un halogène,

les groupes OR7, SR7, NR7R'7, COORy, CONR7R'7, CF3, CN, NRyCOR'y, S02R7, The present invention therefore relates to a hair care composition containing in a physiologically acceptable medium an effective amount of a styryl-pyrazole compound of formula (I) or a salt thereof:

in which: R1, R2, R4 and R5, which are identical or different, are chosen from hydrogen, a halogen,

the groups OR7, SR7, NR7R'7, COORy, CONR7R'7, CF3, CN, NRyCOR'y, SO2R7,

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alkyle, saturés ou insaturés, linéaires ou ramifiés, en Cl-C20, les cycles de 4 à 7 atomes, saturés ou insaturés, contenant éventuellement au moins un hétéroatome, ces cycles pouvant être séparés ou accolés, les radicaux alkyle et les cycles pouvant,

en outre, être substitués par au moins un substituant A1, avec R7, R'7, R"7 et Ruz, désignant indépendamment l'hydrogène, un radical alkyle en C1-C20, linéaire ou ramifié ou un cycle de 4 à 7 atomes, contenant éventuellement au moins un hétéroatome, isolé ou accolé à un autre cycle, le radical alkyle ou lesdits cycles étant saturés ou non et éventuellement substitués par au moins un substituant A2 ,

- R3 est choisi parmi CN, COOR8, CONR8R'8, COR8, SO2R8, S02NRBR'8, avec R8 et R'8 désignant indépendamment l'hydrogène, un radical alkyle en Cl-C20, linéaire ou ramifié ou un cycle de 4 à 7 atomes, isolé ou accolé à un autre cycle et contenant éventuellement au moins un hétéroatome, le radical alkyle ou lesdits cycles étant saturés ou non et éventuellement substitués par un au moins un substituant A3 ; - R6 est choisi parmi l'hydrogène, les groupes COORg, COR9, CSR9, COSR9,

CONRgR'9, S02R9, S02NRgR'9, les radicaux alkyle en C1-C20, linéaires ou ramifiés, saturés ou non et les cycles de 4 à 7 atomes, saturés ou insaturés, contenant éventuellement au moins un hétéroatome, ces cycles pouvant être séparés ou accolés, les radicaux alkyle et les cycles pouvant, en outre, être, substitués par au moins un substituant A4, avec Rg et R'9 identiques ou différents désignant

l'hydrogène, un radical alkyle en C1-C20, linéaire ou ramifié ou un cycle de 4 à 7 atomes, contenant éventuellement au moins un hétéroatome, isolé ou accolé à un autre cycle, le radical alkyle ou lesdits cycles étant saturés ou non et éventuellement substitués par au moins un substituant A5 ; - Ai, A2, A3, A4 et A5 étant indépendamment choisis parmi les halogènes, les groupes

OR,o, SR,O, NR,oR'lo, COOR1o, CH2COORio, CONR1OR'1O, CF3, CN, NR107COR'10, S02R,o, S02NR,QR'lo, NR,OS02R'lo, COR,O, CSR,O, OCOR,O, COSR,O, SCOR,O, CSNR,oR'lo, NR10CONR'10R"io, NR,OC(=NR'10)NR",OR"'10, NR1oCSNR',oR"io, NR1OCSR'1O, avec Rio, R'lo, R"1O et R'''10 identiques ou différents désignant l'hydrogène, un radical alkyle en Ci-C2o, linéaire ou ramifié ou un cycle de 4 à 7 atomes, contenant éventuellement au moins un hétéroatome, isolé ou accolé à un autre cycle, le radical alkyle ou lesdits cycles étant saturés ou non. S02NR7R'7, NR7SO2R'7, COR7, CSR7, OCOR7, COSR7, SCOR7, CSNR7R'7, NR7CONR'7R "7, NR7C (= NR'7) NR" 7R '"7, NR7CSR'7, NR7CSNR'7R" 7, the radicals

linear or branched C 1 -C 20 alkyl, saturated or unsaturated, saturated or unsaturated rings of 4 to 7 atoms, optionally containing at least one heteroatom, these rings being separable or contiguous, the alkyl radicals and the rings being able to

in addition, be substituted by at least one substituent A1, with R7, R'7, R "7 and Ruz, independently denoting hydrogen, a linear or branched C1-C20 alkyl radical or a ring of 4 to 7 atoms , optionally containing at least one heteroatom, isolated or attached to another ring, the alkyl radical or said rings being saturated or unsaturated and optionally substituted with at least one substituent A2,

R3 is chosen from CN, COOR8, CONR8R'8, COR8, SO2R8, SO2NRBR'8, with R8 and R'8 independently denoting hydrogen, a linear or branched C1-C20 alkyl radical or a ring of from 4 to 7 atoms, isolated or attached to another ring and optionally containing at least one heteroatom, the alkyl radical or said rings being saturated or not and optionally substituted with at least one substituent A3; R6 is chosen from hydrogen, COORg, COR9, CSR9 and COSR9 groups;

CONRgR'9, SO2R9, SO2NRgR'9, linear or branched, saturated or unsaturated C1-C20 alkyl radicals and saturated or unsaturated 4 to 7 atom rings, optionally containing at least one heteroatom, these rings being separable or contiguous, the alkyl radicals and rings may, in addition, be substituted by at least one substituent A4, with Rg and R'9 identical or different designating

hydrogen, a linear or branched C1-C20 alkyl radical or a ring of 4 to 7 atoms, optionally containing at least one heteroatom, isolated or attached to another ring, the alkyl radical or said rings being saturated or not and optionally substituted with at least one substituent A5; Where A1, A2, A3, A4 and A5 are independently selected from halogens, the groups

OR, o, SR, O, NR, oR'lo, COOR1o, CH2COORio, CONR1OR'10, CF3, CN, NR107COR'10, SO2R, o, SO2NR, QRlo, NR, OS02R'lo, COR, O, CSR, O, OCOR, O, COSR, O, SCOR, O, CSNR, oR'lo, NR10CONR'10R "io, NR, OC (= NR'10) NR", OR "'10, NR1oCSNR ', oR" io, NR1OCSR'10, with R10, R'lo, R "10 and R '''10 being identical or different, denoting hydrogen, a C1-C20 alkyl radical, linear or branched, or a ring of 4 to 7 atoms, optionally containing at least one heteroatom, isolated or attached to another ring, the alkyl radical or said rings being saturated or not.

The invention also relates to the use of at least one pyrazole compound of formula (1) or of one of its salts, as defined above, as an agent for inducing and / or stimulating the growth of human beings' hair. humans and / or curb their fall and / or increase their density.

The invention also relates to the cosmetic use of at least one pyrazole compound of formula (I) or a salt thereof in a human hair care cosmetic composition for reducing hair loss and / or or increase their density. It also relates to the use of at least one pyrazole compound of formula (1) or of one of its salts for the preparation of a hair composition for human beings intended to induce and / or stimulate the growth of hair and / or curb their fall and / or increase their density.

In particular, the invention relates to the cosmetic use of at least one pyrazole compound of formula (1) or of one of its salts in a cosmetic composition for the care of human hair or for the preparation of a human hair composition for or for treating androgenic alopecia. Thus, this composition makes it possible to maintain the hair in good condition and / or to fight against the natural fall of men's hair.

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 The subject of the invention is also the use of at least one pyrazole compound of formula (I) or one of its salts as an inhibitor of 15-hydroxyprostaglandin dehydrogenase. It also relates to the use of at least one pyrazole compound of formula (I) or a salt thereof for the manufacture of a composition for treating disorders related to 15-hydroxyprostaglandin dehydrogenase in humans. 'To be human.

By inhibitor of 15-hydroxyprostaglandin dehydrogenase is meant a compound of formula (1) which has little or no inhibitory effect on prostaglandin synthesis, in particular on the synthesis of PGF2-a or PGE2. According to a particular embodiment of the invention, the 15-PGDH inhibitor is little or no inhibitor of prostaglandin synthase (PGF synthase).

Indeed, the Applicant has now unexpectedly found that PGF synthase is also expressed in the dermal papilla. Maintaining an effective amount of prostaglandins at the site of action therefore results from a complex biological balance between the synthesis and degradation of these molecules. The exogenous supply of compounds that inhibit catabolism will therefore be less effective if this activity is combined with inhibition of synthesis.

In the rest of the text, and except express mention, the use of the term compound of formula (1) should be understood as meaning both the compound of formula (I) in nonionic form as in salt form.

respectivement de la PGFsynthase, IC5ofs, et de la 15-PGDH, ICsoan, est d'au moins 3:1, avantageusement supérieur ou égal à 5:1. Les composés préférés de l'invention présentent un ratio IC50fs/IC50dh supérieur ou égal à 10:1, et en particulier supérieur ou égal à 15. Advantageously, the compounds of formula (1) have a 15-PGDH inhibitory activity which is greater than the inhibitory activity of PGF synthase. In particular, the ratio between inhibitory concentrations of 50% of enzymatic activity.

respectively PGF synthase, IC5ofs, and 15-PGDH, ICsoan, is at least 3: 1, advantageously greater than or equal to 5: 1. The preferred compounds of the invention have an IC50fs / IC50dh ratio greater than or equal to 10: 1, and in particular greater than or equal to 15.

"At least one" according to the invention means one or more (2,3 or more). In particular, the composition may contain one or more compounds of formula (1). This or these compounds may be cis or trans isomers or a mixture of cis / trans isomers. In particular, the aromatic ring may be in a cis or trans position with respect to the pyrazole ring. This or these compounds may also be in tautomeric form. They may also be enantiomers and / or diastereoisomers or a mixture of these isomers, in particular a racemic mixture.

According to the invention, the rings employed for R 1 to R 10, R '7, R "7, R"' 7, R 's, Ru, R' 10, R "10 and R" "have from 4 to 7 atoms and better from 5 to 6 atoms. They can be saturated or unsaturated and optionally include one or more heteroatoms such as S, N, O or their combinations. They may be alone or contiguous to another cycle that may be the same or different. As saturated carbon rings that may be used, mention may be made of the cyclopentyl or cyclohexyl radical. As heterocycle, mention may be made of the pyridine, piperidine, morpholine, pyrrole, furan and thiazole rings. As unsaturated carbon rings, mention may be made of the phenyl and naphthyl radicals. In addition, these rings may be substituted with a substituent having the definition indicated above for A. Advantageously, when R 6 has one or more heteroatoms, the linkage with the nitrogen of the pyrazole ring is in the form of an N-C bond.

radicaux alkyle ou aryle, à savoir A, à A5 sont les atomes d'halogène et notamment les atomes de chlore, brome, iode ou fluor, de préférence les atomes de chlore ou les According to one embodiment of the invention, the substituent or substituents carried by the

alkyl or aryl radicals, namely A, to A5 are the halogen atoms and in particular the chlorine, bromine, iodine or fluorine atoms, preferably the chlorine atoms or the

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 linear or branched C1-C20 alkyl radicals or perfluorinated alkyl radicals. As examples of perfluorinated alkyl radicals which may be used, mention may be made of CF.sub.3. As an example of an alkyl radical which can be used according to the invention, mention may be made of methyl, ethyl, iso-propyl, n-butyl and n-hexyl.

According to the invention, the compounds of formula (I) (or their salt (s)) are in isolated form, that is to say nonpolymeric. In addition, R 1 and R 2 can be located in any position of the phenyl ring and in particular in the ortho position of the branch of the pyrazole part.

Advantageously, R1 and R2 do not simultaneously represent OR? Preferably, at least one of R1 and R2 represents a hydrogen atom, a halogen atom and especially a chlorine atom. In particular, R1 and R2 represent a chlorine atom.

Advantageously, R3 represents CN, COOR8, CONRsR's, COR8 and for example CN.

l'un de l'autre CH2CH20R,O, NH2, H ou CN, R10 représentant par exemple H Avantageusement, R6 représente CH2CH20R,o et en particulier CH2CH20H. De préférence, R4 représente NH2 ou H. Selon un mode avantageux, R5 représente CN ou H. According to one embodiment of the invention, R4, R5, R6 represent independently

CH2CH20R, O, NH2, H or CN, R10 representing for example H Advantageously, R6 represents CH2CH20R, o and in particular CH2CH20H. Preferably, R4 is NH2 or H. In an advantageous embodiment, R5 is CN or H.

By salts of compound of formula (I) is meant according to the invention, the organic or inorganic salts of a compound of formula (1).

ou de potassium ainsi que les sels de zinc (Zn2+), de calcium (Ca2+), de cuivre (C U2*), de fer (Fe2+), de strontium (Sr2+), de magnésium (Mg2+) et de manganèse (Mn2+) , les hydroxydes et les carbonates. As inorganic salts that can be used according to the invention, mention may be made of sodium salts

or potassium and salts of zinc (Zn2 +), calcium (Ca2 +), copper (C U2 *), iron (Fe2 +), strontium (Sr2 +), magnesium (Mg2 +) and manganese (Mn2 +) , hydroxides and carbonates.

The organic salts which can be used according to the invention are, for example, the salts of t-ethanolamine, mono-ethanolamine, di-ethanolamine, hexadecylamine, N, N, N ', N'tetrakis (2-hydroxypropyl) ethylenediamine, tris hydroxymethyl aminomethane.

Examples of pyrazole compounds of formula (1) that can be used in the invention include the following compounds: Compound 1:

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5
Composé 3 :

10 Composé 4 :

Compound 2:

5
Compound 3:

Compound 4:

Compound 5- 15

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 The compounds of formula (1) or their salts are known as such. They can be manufactured by the condensation of a benzaldehyde, optionally substituted with a pyrazole substituted by an activated methylene, by one of the functions nitrile, acid, ester, amide or ketone. The elimination of water is carried out simultaneously by azeotropic distillation and the installation of a "Dean-Stark" type apparatus. This kind of preparation is known to those skilled in the art of EP 0 245 825. These compounds are in the form of a solid and in particular in powder form or in liquid form.

To the applicant's knowledge, no document of the prior art declines nor suggests that the pyrazole compounds of formula (I) or a salt thereof have the property of inducing and / or stimulating hair growth and / or to curb their fall or that these compounds can be used topically to increase the density of the hair.

The effective amount of a compound of formula (I) or a salt thereof is the amount necessary to achieve the desired result (i.e., increasing hair density). Those skilled in the art are therefore able to evaluate this effective amount which depends on the nature of the compound used, the person to whom it is applied, and the time of this application.

In the rest of the text, and unless otherwise indicated, the amounts of the various ingredients of the composition are given as a percentage by weight relative to the total weight of the composition.

To give an order of magnitude, according to the invention, the compound of formula (I) or of one of its salts can be used in an amount representing 10-3% to 5% of the total weight of the composition and preferably in an amount representing from 10-2% to 2% of the total weight of the composition, for example from 0.5 to 2%.

The composition of the invention may be for cosmetic or pharmaceutical use. Preferably, the composition of the invention is for cosmetic use. Also, the composition must contain a physiologically acceptable medium that is non-toxic and may be applied to the skin, the integuments or the lips of human beings. By "cosmetic" is meant in the sense of the invention a composition of appearance, smell and pleasant touch.

The compound of formula (1) or one of its salts may be used in a composition which must be ingested, injected or applied to the skin (on any cutaneous area to be treated).

According to the invention, the compound of formula (I) or one of its salts can be used orally in an amount of 0.1 to 300 mg per day, for example 5 to 10 mg / day.

A preferred composition of the invention is a composition for cosmetic use and in particular for topical application to the skin, and more particularly to the scalp.

This composition can be in any known galenic forms adapted to the mode of use.

For topical application to the skin, the composition may have the form of an aqueous or alcoholic or aqueous-alcoholic solution or suspension or of an oily suspension, of an emulsion of more or less fluid consistency and in particular liquid or semi-fluid. liquid, obtained by dispersion of a fatty phase in an aqueous phase (O / W) or conversely (W / O), of a solid (O / W) or (W / O) emulsion, of an aqueous gel,

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 hydro-alcoholic or oily more or less fluid or solid, a free or compacted powder to be used as such or to incorporate in a physiologically acceptable medium, or microcapsules or microparticles, vesicular dispersions of ionic and / or nonionic type . It can thus be in the form of a lotion, serum, milk, O / W or W / O cream, ointment, ointment, balm, patch, soaked pad.

It is also possible to envisage a composition in the form of a foam or in the form of a spray or an aerosol then comprising a propellant under pressure. In particular, the composition for application to the scalp or the hair may be in the form of a lotion of hair care, for example daily or bi-weekly application, shampoo or hair conditioner, in particular bi-weekly or weekly application, liquid soap or solid scalp cleansing daily application, a product shaping the hairstyle (lacquer, product for setting, styling gel), a mask, a cream or a foaming gel for cleaning the hair. It can still be in the form of hair dye or mascara to be applied by brush or comb.

For an injection-use composition, the composition may be in the form of an aqueous lotion or an oily suspension. For oral use, the composition may be in the form of capsules, granules, oral syrups or tablets.

According to a particular embodiment, the composition according to the invention is in the form of a hair cream or lotion, a shampoo or a hair conditioner.

The amounts of the various constituents of the composition according to the invention are those generally used in the fields under consideration. In addition, these compositions are prepared according to the usual methods.

When the composition is an emulsion, the proportion of the fatty phase may range from 2% to 80% by weight, and preferably from 5% to 50% by weight relative to the total weight of the composition. The aqueous phase is adjusted as a function of the content of the fatty phase and of the compound (s) (I) as well as that of any additional ingredients, to obtain 100% by weight. In practice, the aqueous phase represents from 5 to 99.9% of the weight of the total weight of the composition.

The fatty phase may contain fatty or oily compounds which are liquid at ambient temperature (25 ° C.) and atmospheric pressure (760 mmHg), generally called oils. These oils may or may not be compatible with each other and form a macroscopically homogeneous liquid fatty phase or a two- or three-phase system.

The fatty phase may, in addition to the oils, contain waxes, gums, lipophilic polymers, "pasty" or viscous products containing solid parts and liquid parts.

proportion à l'eau comme les alcools inférieurs en Cl à C8 tel que l'éthanol, l'isopropanol, les polyols comme le propylène glycol, le glycérol, le sorbitol ou encore l'acétone ou l'éther. The aqueous phase contains water and optionally a miscible ingredient in all

proportion to water, such as lower C1 to C8 alcohols such as ethanol, isopropanol, polyols such as propylene glycol, glycerol, sorbitol, or acetone or ether.

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The emulsifiers and co-emulsifiers used to obtain a composition in emulsion form are those generally used in the cosmetic and pharmaceutical fields. Their nature is, moreover, a function of the meaning of the emulsion. In practice, the emulsifier and optionally the co-emulsifier are present in the composition in a proportion ranging from 0.1% to 30% by weight, preferably from 0.5% to 20% by weight and better still from 1% to 8%. The emulsion may further contain lipid vesicles and in particular liposomes.

When the composition is in the form of an oily solution or gel, the fatty phase may represent more than 90% of the total weight of the composition.

Advantageously, the composition is an aqueous, alcoholic or hydro-alcoholic solution or suspension and better a water / ethanol solution or suspension. The alcohol fraction may represent from 5 to 99.9% and especially from 8 to 80%.

The composition of the invention may comprise, in addition, other ingredients usually used in the relevant fields, chosen from solvents, thickeners or gelling agents of aqueous phase or oily phase, the dyestuffs soluble in the medium of the composition solid particles of the fillers or pigments type, antioxidants, preservatives, perfumes, electrolytes, neutralizers, U blocking agents. V. like sunscreens, cosmetic and pharmaceutical active ingredients, their blends. These additives may be present in the composition according to the amounts generally used in the cosmetic and dermatological field and in particular in a proportion of from 0.01 to 50% of the total weight of the composition and better still from 0.1 to 20% and for example from 0 to , 1 to 10%.

Of course, those skilled in the art will take care to choose the possible additional additives and / or their quantity in such a way that the advantageous properties of the composition according to the invention, namely the inhibition of 15-PGDH in particular or the increase of the capillary density, are not or not substantially, altered by the addition envisaged.

As oils that can be used in the invention, mention may be made of oils of mineral origin (vaseline oil, hydrogenated isoparaffin), oils of vegetable origin (liquid fraction of shea butter, sunflower oil, apricot oil, alcohol or fatty acid), oils of animal origin (perhydrosqualene), synthetic oils (fatty acid ester, Purcellin oil), silicone oils (linear or cyclic polydimethylsiloxane, phenyltrimethicone) and fluorinated oils (perfluoropolyethers). As waxes, mention may be made of silicone waxes, beeswax, carnauba or paraffin waxes, and polyethylene waxes.

As emulsifiers that can be used in the invention, mention may be made, for example, of glycerol stearate or laurate, sorbitol stearates or oleates, alkyl dimethiconecopolyol (with alkyl # 8) and their mixtures for an W / O emulsion. It is also possible to use the polyethylene glycol monostearate or monolaurate, polyoxyethylenated sorbitol stearate or oleate, dimethiconecopolyols and mixtures thereof for an O / W emulsion.

As hydrophilic gelling agents that may be used in the invention, mention may be made of carboxyvinyl polymers (carbomer), acrylic copolymers such as acrylate / alkylacrylate copolymers, polyacrylamides, polysaccharides such as hydroxypropylcellulose, natural gums and clays, and, as lipophilic gelling agents, mention may be made of modified clays such as Bentones, metal salts of fatty acids such as aluminum stearates, hydrophobic treated silica, ethylcellulose, and mixtures thereof.

<Desc / Clms Page number 11>

 The composition may contain an active ingredient other than the compounds of formula (I) which may be hydrophilic and chosen from proteins, protein hydrolysates, amino acids, polyols, urea, allantoin, sugars and derivatives sugar, water-soluble vitamins, vegetable extracts (those of Iridaceae or soya) and hydroxy acids; or lipophilic, and selected from retinol (vitamin A) and its derivatives including ester (retinol palmitate), tocopherol (vitamin E) and its derivatives (tocopherol acetate), essential fatty acids, ceramides, essential oils, salicylic acid and its derivatives such as 5-n-octanoylsalicylic acid, esters of hydroxy acids, phospholipids such as lecithin, and mixtures thereof.

According to one particular embodiment of the invention, it is possible to associate with the compound of formula (1) or one of its salts, additional compounds that promote regrowth and / or limit hair loss. These additional compounds are chosen in particular from the lipoxygenase inhibitors as described in EP 0648488, the inhibitors of bradykinin described in particular in EP 0845700, the prostaglandins and their derivatives, in particular those described in WO 98/33497, WO 95/11003, JP 97- 100091, JP 96-134242, Prostaglandin receptor agonists or antagonists, non-prostanoid prostaglandin analogs as described in EP 1175891 and EP 1175890, WO 01/74307, WO 01/74313, WO 01/74314, WO 01 / 74315 or WO 01/72268, their mixtures.

Other additional compounds promoting hair growth that may be present in the composition according to the invention include vasodilators, antiandrogens, cyclosporins and their analogues, antimicrobials and antifungals, anti-inflammatories, retinoids, their mixtures.

Vasodilators which may be used include potassium channel agonists including minoxidil as well as the compounds described in US Pat. Nos. 3,382,247, 5,756,992, 5,772,900, 5,600,443, 4,666,994, 5,480,858, 97,374, cromakalim, nicorandil and diaxozide, alone or in combination.

Useful anti-androgens include steroidal and non-steroidal 5α-reductase inhibitors, such as finasteride and the compounds described in US 5,516,779, cyprosterone acetate, azelaic acid, its salts and derivatives and the compounds described. in US 5,480,913, flutamide and the compounds described in US 5,411,981, 5,565,467 and 4,910,226.

The anti-microbial or antifungal compounds may be chosen from selenium derivatives, octopirox, ketoconazole, triclocarban, triclosan, pyrithione zinc, itraconazole, asiatic acid, hinokitiol, mipirocine, tetracyclines, especially erythromycin and the compounds described in EP 0680745, clinycin hydrochloride, benzoyl or benzyl peroxide and minocycline.

The anti-inflammatory drugs may be selected from steroidal anti-inflammatory agents such as glucocorticoids, corticosteroids (for example: hydrocortisone) and non-steroidal anti-inflammatory drugs such as glycyrrhetinic acid and a-bisabolol, benzydamine, and Salicylic acid and the compounds described in EP 0770399, WO 94/06434 and FR 2268523.

l'aminexil, le 6-0-[(9Z, 1 2Z)-octadéca-9,1 2-diènoyl]hexopyran ose, le chlorure de benzalkonium, le chlorure de benzéthonium, le phénol, l'#stradiol, le maléate de The retinoids may be chosen from isotretinoin, acitretin and tazarotene. Other active compounds that promote the growth and / or limit the hair loss that can be used in combination with the compound of formula (1) include

aminexil, 6-0 - [(9Z, 12Z) -octadeca-9,1 2 -dienoyl] hexopyranose, benzalkonium chloride, benzethonium chloride, phenol, # stradiol, maleate,

<Desc / Clms Page number 12>

 chlorpheniramine, chlorophyllin derivatives, cholesterol, cysteine, methionine, menthol, peppermint oil, calcium panthotenate, panthenol, resorcinol, protein kinase C activators, glycosidase inhibitors , glycosaminoglycanase inhibitors, pyroglutamic acid esters, hexosaccharide or acyl-hexosaccharic acids, substituted aryl ethenes, N-acylamino acids, flavonoids, ascomycin derivatives and analogs, histamine antagonists , saponins, proteoglycanase inhibitors, estrogen agonists and antagonists, pseudoterines, cytokines and promoters of growth factors, IL-1 or IL-6 inhibitors, IL-1 promoters, 1 0, TNF inhibitors, hydroxy acids, benzophenones, hydantoin, retinoic acid; vitamins such as vitamin D, vitamin B12 analogues and panthotenol; antipruritic agents such as thenaldine, trimeprazine or cyproheptadine; antiparasitics, particularly metronidazole, crotamiton or pyrethroids; antifungals, in particular octopirox and compounds belonging to the class of imidazoles such as econazole, ketoconazole or miconazole or their salts; nicotinic acid esters, including in particular tocopherol nicotinate, benzyl nicotinate and C1-C6 alkyl nicotinates such as methyl or hexyl nicotinates; calcium antagonists, such as cinnarizine, diltiazem, nimodipine, verapamil and nifedipine, hormones such as estriol or its analogs, thyroxine and its salts, progesterone; triterpenes such as ursolic acid and the compounds described in US 5529769, US 5468888, US 5631282; antiandrogens, such as oxendolone, spironolactone, diethylstilbestrol and flutamide; their mixtures.

Advantageously, the composition according to the invention will comprise at least one inhibitor of 15-PGDH as defined above and at least one prostaglandin or a prostaglandin derivative, for example prostaglandins of series 2, in particular PGF2-a and PGE2 in the form of salines or esters (eg isopropyl esters), their derivatives such as 16,16 dimethyl PGE2, 17 phenyl PGE2, 16,16 dimethyl PGF2-a, 17 phenyl PGF2-a prostaglandins of series 1 such as 11 deoxy prostaglandin E1, 1 deoxy prostaglandin E1 in saline or ester form, their analogues in particular latanoprost, travoprost, fluprostenol, cloprostenol, viprostol, butaprost, misoprostol, their salts or their esters.

Preferably, the composition contains at least one non-prostanoic agonist of the EP2 and / or EP4 receptors, in particular as described in EP 1175892.

It is also conceivable that the composition comprising at least the compound of formula (I) or one of its salts is in liposome form, such as in particular described in WO 94/22468. Thus, the liposome encapsulated compound can be delivered selectively to the hair follicle.

The composition according to the invention can be applied to the alopecic areas of the scalp and hair of an individual, and possibly left in contact for several hours and possibly rinsed.

For example, the composition containing an effective amount of a compound of formula (1) or a salt thereof may be applied in the evening, kept in contact overnight and optionally shampooed in the morning. These applications may be renewed daily for one or more months depending on the individuals. Thus, the subject of the present invention is also a process for the cosmetic treatment of the hair and / or the scalp, intended to stimulate the growth of the hair of being human and / braking their fall, characterized by the fact that it consists of

<Desc / Clms Page number 13>

 applying to the hair and / or the scalp, a cosmetic composition comprising an effective amount of at least one compound of formula (I) or a salt thereof, to leave the latter in contact with the hair and / or the scalp, and possibly rinsing the hair and / or the scalp.

This treatment method has the characteristics of a cosmetic process insofar as it makes it possible to improve the aesthetics of the hair by giving them greater vigor and an improved appearance. In addition, it can be used daily for several months.

Advantageously, in the. method according to the invention is applied to the areas to be treated of the scalp between 5 and 500 l of a solution or composition as defined above, comprising from 0.001% to 5% of 15-PGDH inhibitor.

Examples of embodiments of the invention which will not in any way limit its scope will now be given by way of illustration.

 EXAMPLE 1: Evidence of the specific inhibitory properties of 15-PGDH of the compounds of formula (1).

 1) Test on 15-PGDH The 15-PGDH enzyme is obtained as described in application FR 02/05067 filed in the name of L'Oréal, in suspension in a medium adapted to a concentration of 0.3 mg / ml and then blocked at -80 C. For testing purposes, this suspension is thawed and stored in ice.

In addition, a 100 mM Tris buffer, pH = 7.4, containing 0.1 mM of dithiothreitol (D5545, Sigma-Aldrich, L'Isle d'Abeau Chesne, BP 701.38297, Saint Quentin Fallavier), 1, is prepared. 5 mM of p-NAD (N6522, Sigma-Aldrich, The Abes Chesne Island, BP 701, 38297, Saint Quentin Fallavier), 50 M of Prostaglandin E2 (P4172, SigmaAldrich, L'Isle d'Abeau Chesne, BP 701, 38297, Saint Quentin Fallavier).

In the tank of a spectrophotometer (Perkin-Elmer, Lambda 2) thermostated at 37 C, whose measuring wavelength is set at 340 nm, are introduced 0.965 ml of this buffer (previously heated to 37 C). 0.035 ml of 37 C enzyme suspension are introduced into the cuvette at the same time as the recording (corresponding to an increase in the optical density at 340 nm). The maximum reaction rate is recorded.

The test values (containing the compounds (I)) are compared with the control value (without compound (I)), the results indicated represent the concentration at which the compound (1) inhibits 50% of the enzymatic activity of the compound. PGDH, noted IC50dh.

2) Test on PGF Synthase
The PGFS enzyme is obtained as described in document FR-A-02/05067, at the concentration of 0.5 mg / ml, suspended in a suitable medium, and blocked at -80 ° C. For the purposes of the test, this suspension is thawed and stored in the ice.

On the other hand, a tris 100, mM, pH = 6.5 buffer containing 20 M of 9,10 phenanthrene quinone * (P2896, Sigma-Aldrich, is prepared in a brown bottle (protected from light).
The Abes Chesne isle, BP 701, 38297, Saint Quentin Fallavier) and 100 M ssNADPH (N1630, Sigma-Aldrich, The Isle of Abeau Chesne, BP 701, 38297, Saint Quentin Fallavier).

<Desc / Clms Page number 14>

* A stock solution titrant 1 mM is prepared in absolute ethanol, brought to 40 C, the bottle is placed in an ultrasonic tank to facilitate the solubilization of the product.

composé (I) inhibe 50% de l'activité enzymatique de PGFS, notée IC50f,.

composé structure Inhibition de 15-PGDH Inhibition de PGF IC50dh M synthase ICSOfs LM OH 1 fJ W,N 3 > 50 nc \y~2 CH CN Cil cl Il ressort de ce tableau que le rapport IC50fs/IC50dh est > 16,6. Le composé 1 a donc une activité inhibitrice sélective vis-à-vis de 15-PGDH par rapport à PGF synthase Les compositions ci-après sont obtenues par les techniques habituelles couramment utilisées dans le domaine cosmétique ou pharmaceutique. In the tank of a spectrophotometer (Perkin-Elmer, Lambda 2) thermostated at 37 C, whose measuring wavelength is set at 340 nm are introduced 0.950 ml of this buffer (previously heated to 37 C). 0.05 ml of enzymatic suspension at 37 ° C. are introduced into the tank at the same time as the recording (corresponding to a drop in the optical density at 340 nm). The maximum reaction rate is recorded. The test values (containing compound (I)) are compared with the control value (without compound (I)); the results shown represent the concentration at which the

Compound (I) inhibits 50% of the enzyme activity of PGFS, denoted IC50f ,.

Structure compound Inhibition of 15-PGDH Inhibition of PGF IC50dh M synthase ICSOfs LM OH 1 fJ W, N 3> 50 nc \ y ~ 2 CH CN Cil cl It is apparent from this table that the ratio IC50fs / IC50dh is> 16.6. Compound 1 therefore has a selective inhibitory activity against 15-PGDH relative to PGF synthase. The compositions below are obtained by the usual techniques commonly used in the cosmetics or pharmaceutical field.

EXAMPLE 2: Hair lotion - Compound 1 0.80 g - Propylene glycol 10.00 g - Isopropyl alcohol qs 100.00 g This lotion is applied to the scalp, once or twice a day, at a rate of 1 ml per ml. application, gently massaging the scalp to penetrate the asset. The hair is then dried in the open air. This lotion helps reduce hair loss and promote their regrowth.

EXAMPLE 3 Hair lotion - Compound 2 1.00 g - Propylene glycol 30.00 g - Ethyl alcohol 40.00 g - Water qs 100.00 g This lotion is applied to the scalp, once or twice a day, at the rate of 1 ml per application, gently massaging the scalp to penetrate the active The hair is then dried in the open air.

<Desc / Clms Page number 15>

EXAMPLE 4: Hair lotion - Compound 1 1 g - Ethyl alcohol 40.00 g - HCl qs (*) - Water qs 100.00 g (*) enough to neutralize the amine function carried on the pyrazole nucleus This lotion is applied to the scalp, once or twice a day, at a rate of 1 ml per application by gently massaging the scalp to penetrate the active

Claims (35)

 OR, o, SR, o, NR, oR'lo, COOR1o, CH2COORio, CONR, oR'lo, CF3, CN, NR107COR'io, SO2R, o, SO2NR, oR'lo, NRiOSO2R'lo, COR, O, CSR1O, OCOR, O, COSR1O, SCOR, O, CSNR, oR'lo, NR10CONR'10R "io, NRIOC (= NR'10) NR", OR "lo, NR10CSNR'10R" 10, NR10CSR'10, with Rlo, R'lo, R "and Roo identical or different designating hydrogen, a linear or branched C 1 -C 20 alkyl radical or a cycle of 4 to 7

 CONRgR'g, SO2R9, SO2NRgR'9, linear or branched, saturated or unsaturated Croc20 alkyl radicals and saturated or unsaturated 4 to 7 atom rings, optionally containing at least one heteroatom, which rings can be separated or contiguous , the alkyl radicals and the rings may, in addition, be substituted by at least one substituent A4, with Rg and R'9 identical or different, denoting hydrogen, a linear or branched C1-C20 alkyl radical, or a ring from 4 to 7 atoms, optionally containing at least one heteroatom, isolated or attached to another ring, the alkyl radical or said rings being saturated or not and optionally substituted with at least one substituent A5; - A1, A2, A3, A4 and A5 being independently selected from halogens, the groups

 R3 is chosen from CN, COOR8, CONR8R'8, COR8, SO2R8, SO2NR8R'8, with R8 and R'8 independently denoting hydrogen or a linear or branched C1-C20 alkyl radical, or a ring of from 4 to 7 atoms, isolated or attached to another ring and optionally containing at least one heteroatom, the alkyl radical or said rings being saturated or not and optionally substituted by at least one substituent A3, - R6 is chosen from hydrogen, the groups COOR9, COR9, CSR9, COSR9,

NR7CONR'7R "7, NR7C (= NR'7) NR" 7R "'7, NR7CSR'7, NR7CSNR'7R" 7, saturated or unsaturated, linear or branched C1-C20 alkyl radicals, 4 to 7 atoms, saturated or unsaturated, optionally containing at least one heteroatom, these rings being separable or contiguous, the alkyl radicals and the rings may, in addition, be substituted by at least one substituent A1, with R7, R'7 , R "7 and R '' '7 independently denoting hydrogen, a linear or branched C1-C20 alkyl radical or a ring of 4 to 7 atoms, optionally containing at least one heteroatom, isolated or attached to another ring the alkyl radical or said rings being saturated or not and optionally substituted with at least one substituent A2, S02NR7R'7, NR7SO2R'7, COR7, CSR7, OCOR7, COSR7, SCOR7, CSNR7R'7,  in which: R1, R2, R4 and R5, which are identical or different, are chosen from hydrogen, a halogen, the groups OR7, SR7, NR7R'7, COOR7, CONR7R'7, CF3, CN, NR7COR'7, SO2R7,

 1. Use of an effective amount of at least one styryl-pyrazole compound of formula (I) or a salt thereof, <Desc / Clms Page number 17>  atoms, optionally containing at least one heteroatom, isolated or attached to another ring, the alkyl radical or said rings being saturated or not, as an agent for inducing and / or stimulating the growth of human hair and / or curbing their fall and / or increase their density. 2. Cosmetic use of at least one styryl-pyrazole compound of formula (I) or a salt thereof

 in which :

 - R1 'R2, R4 and R5 identical or different are selected from hydrogen, halogen, OR7, SR7, NR7R'7, COOR7, CONR7R'7, CF3, CN, NR7COR'7, SO2R7.  OR, O, SR, O, NR, OH, COOR1O, CH2COORIO, CONR, OR'lo, CF3, CN, NR107COR ', (), SO2R, O, SO2NR, oR'lo, NR1SO2R'lo, COR1o, CSR1O, OCOR, O, COSR, O, SCOR, O, CSNR, OR'lo, NR, OCONR ', OR "10, NR1oC (= NR'1o) NR" 1oR' "io, NR1oCSNR'10R" io,

 CONRgR'g, SO2R9, SO2NR9R'9, linear or branched C1-C20 alkyl radicals, saturated or unsaturated, and rings of 4 to 7 atoms, saturated or unsaturated, optionally containing at least one heteroatom, these rings being separable or contiguous, the alkyl radicals and rings may, in addition, be substituted by at least one substituent A4, with Rg and R'g identical or different designating hydrogen, a linear or branched C 1 -C 20 alkyl radical or a ring of 4 to 7 atoms, optionally containing at least one heteroatom, isolated or attached to another ring, the alkyl radical or said rings being saturated or not and optionally substituted with at least one substituent A5; A1, Az, A3, A4 and A5 being independently selected from halogens, the groups

 R3 is chosen from CN, COOR8, CONR8R'8, COR8, SO2R8, SO2NR8R'8, with R8 and R'8 independently denoting hydrogen or a linear or branched C1-C20 alkyl radical or a ring of from 4 to 7 atoms, isolated or attached to another ring and optionally containing at least one heteroatom, the alkyl radical or said rings being saturated or not and optionally substituted by at least one substituent A3, - R6 is chosen from hydrogen, the groups COOR9, COR9, CSR9, COSRg,

 S02NR7R'7, NR7SO2R'7, COR7, CSR7, OCOR7, COSR7, SCOR7, CSNR7R'7, NR7CONR'7R "7, NR7C (= NR'7) NR" 7R '"7, NR7CSR'7, NR7CSNR'7R" 7, linear or branched, saturated or unsaturated C 1 -C 20 alkyl radicals, saturated or unsaturated rings of 4 to 7 atoms, optionally containing at least one heteroatom, these rings being separable or contiguous, alkyl and the rings may, in addition, be substituted by at least one substituent A1, with R7, R'7, R "7 and R '' '7, independently denoting hydrogen, a linear or branched C1-C20 alkyl radical; or a ring of 4 to 7 atoms, optionally containing at least one heteroatom, isolated or attached to another ring, the alkyl radical or said rings being saturated or not and optionally substituted with at least one substituent A2, <Desc / Clms Page number 18>  NR, OCSR'lo, with Rio, R'lo, R "1Q and R''io identical or different designating hydrogen, a linear or branched C 1 -C 20 alkyl radical or a ring of 4 to 7 atoms, containing optionally at least one heteroatom, isolated or attached to another cycle, the alkyl radical or said rings being saturated or not, in a human hair care cosmetic composition to reduce hair loss and / or increase their density and / or or treat androgenic alopecia.

3. Use of at least one styryl-pyrazole compound of formula (I) or a salt thereof

 in which: R1, R2, R4 and R5, which are identical or different, are chosen from hydrogen, a halogen, the groups OR7, SR7, NR7R'7, COOR7, CONR7R'7, CF3, CN, NR7COR'7, SO2R7, S02NR7R'7, NR7SO2R'7, COR7, CSR7, OCOR7, COSR7, SCOR7, CSNR7R'7, NR7CONR'7R "7, NR7C (= NR'7) NR" 7R "" 7, NR7CSR'7, NR7CSNR'7R "7, saturated or unsaturated, linear or branched C1-C20 alkyl radicals, 4 to 7 atoms, saturated or unsaturated, optionally containing at least one heteroatom, these rings being separable or contiguous, the alkyl radicals and the rings may, in addition, be substituted by at least one substituent A1, with R7, R'7 , R "7 and R '' '7, independently denoting hydrogen, a linear or branched C 1 -C 20 alkyl radical or a ring of 4 to 7 atoms, optionally containing at least one heteroatom, isolated or attached to another ring, the alkyl radical or said rings being saturated or not and optionally substituted by at least one substituent A2,

 R3 is chosen from CN, COORs, CONR8R'8, CORS, SO2R8 and SO2NR8R'8, with Rs and R'8 independently denoting hydrogen or a linear or branched C1-C20 alkyl radical or a ring of from 4 to 7 atoms, isolated or attached to another ring and optionally containing at least one heteroatom, the alkyl radical or said rings being saturated or not and optionally substituted with at least one substituent A3; R6 is selected from hydrogen, COOR9, COR9, CSR9, COSRg,

 CONRgR'g, SO2Rg, SO2NRgR'9, linear or branched, saturated or unsaturated C1-C20 alkyl radicals and saturated or unsaturated 4 to 7 atom rings, optionally containing at least one heteroatom, these rings being separable or contiguous, alkyl radicals and rings may further be substituted by at least one substituent A4, with R9 and R'9 the same or different designating hydrogen, a linear or branched C 1 -C 20 alkyl radical or a ring from 4 to 7 atoms, optionally containing at least one heteroatom, isolated or attached to another ring, the alkyl radical or said rings being saturated or not and optionally substituted with at least one substituent A5; - A1, A2, A3, A4 and A5 being independently selected from halogens, the groups

 OR, O, SR, O, NR, oR ', o, COOR1o, CH2COOR10, CONR, OR'lo, CF3, CN, NR107COR', o, SO2R, O, SO2NR, oR ', o, NR, oSO2R', o, COR, O, CSRo, OCOR, O, COSR, O, SCOR, o, <Desc / Clms Page number 19>  CSNR, oR'lo, NR10CONR'10R "io, NR1oC (= NR'1o) NR" 1oR "', NR10CSNR'10R" io, NR1OCSR'10, with Rlo, R', o, R "10 and Roo are identical or different designating hydrogen, a linear or branched C 1 -C 20 alkyl radical or a ring of 4 to 7 atoms, optionally containing at least one heteroatom, isolated or attached to another ring, the alkyl radical or said rings being saturated or unsaturated for the preparation of a human hair composition for inducing and / or stimulating hair growth and / or slowing hair loss and / or increasing hair density, and / or treating androgenic alopecia.

4. Use of at least one styryl-pyrazole compound of formula (1) or of one of its salts,

 in which: R1, R2, R4 and R5, which are identical or different, are chosen from hydrogen, a halogen, the groups OR7, SR7, NR7R'7, COOR7, CONR7R'7, CF3, CN, NR7COR'7, SO2R7, S02NR7R'7, NR7SO2R'7, COR7, CSR7, OCOR7, COSR7, SCOR7, CSNR7R'7, NR7CONR'7R "7, NR7C (= NR'7) NR" 7R "'7, NR7CSR'7, NR7CSNR'7R" 7, alkyl radicals, saturated or unsaturated, linear or branched, in CrC2o, rings of 4 to 7 atoms, saturated or unsaturated, optionally containing at least one heteroatom, these rings being separable or contiguous, the alkyl radicals and the rings being able, in addition, to be substituted by at least one substituent A1, with R7, R'7, R 7 and R '' '7, independently denoting hydrogen, a linear or branched C 1 -C 20 alkyl radical or a ring of 4 to 7 atoms, optionally containing at least one heteroatom, isolated or attached to another ring, the alkyl radical or said rings being saturated or unsaturated and optionally substituted by at least one substituent A2, - R3 is chosen from CN, COORB, CONR8R'8, COR8, SO2R8, SO2NR8R'8, with R8 and R'8 independently denoting hydrogen or a linear or branched C1-C20 alkyl radical or a ring of 4 to 7 atoms, isolated or attached to another cycl e and optionally containing at least one heteroatom, the alkyl radical or said rings being saturated or not and optionally substituted by at least one substituent A3, - R6 is chosen from hydrogen, COOR9, COR9, CSR9, COSRg,

 CONRgR'g, SO2R9, SO2NRgR'9, linear or branched, saturated or unsaturated C1-C20 alkyl radicals and saturated or unsaturated 4 to 7 atom rings, optionally containing at least one heteroatom, these rings being separable or contiguous, alkyl radicals and rings may, in addition, be substituted by at least one substituent A4, with Rg and R'9 identical or different designating hydrogen, a linear or branched C 1 -C 20 alkyl radical or a ring of 4 to 7 atoms, optionally containing at least one heteroatom, isolated or attached to another ring, the alkyl radical or said rings being saturated or not and optionally substituted with at least one substituent A5; <Desc / Clms Page number 20>  CONRgR'g, SO2Rg, SO2NRgR'9, linear or branched, saturated or unsaturated C1-C20 alkyl radicals and saturated or unsaturated 4 to 7 atom rings, optionally containing at least one heteroatom, these rings being separable or contiguous, alkyl radicals and rings may, in addition, be substituted by at least one substituent A4, with Rg and R'9 identical or different designating hydrogen, a linear or branched C 1 -C 20 alkyl radical or a cycle of 4 to 7 atoms, optionally containing at least one heteroatom, isolated or attached to a

 R 3 is chosen from CN, COOR 8, CONR 8 R 8, COR 8, SO 2 R 8 and SO 2 NR 8 R 8, with R 8 and R 8 independently denoting hydrogen or a linear or branched C 1 -C 20 alkyl radical or a ring of 4 to 7 atoms , isolated or fused to a ring and optionally containing at least one heteroatom, the alkyl radical or said rings being saturated or not and optionally substituted by at least one substituent A3, - R6 is chosen from hydrogen, COOR9 groups, CORg, CSR9, COSR9,

NR7CONR'7R "7, NR7C (= NR'7) NR" 7R "'7, NR7CSR'7, NR7CSNR'7R" 7, saturated or unsaturated, linear or branched C1-C20 alkyl radicals, 4 to 7 atoms, saturated or unsaturated, optionally containing at least one heteroatom, these rings being separable or contiguous, the alkyl radicals and the rings may, in addition, be substituted by at least one substituent A1, with R7, R'7 . R "7 and R '' '7, independently denoting hydrogen, a linear or branched C 1 -C 20 alkyl radical or a ring of 4 to 7 atoms, optionally containing at least one heteroatom, isolated or attached to another ring the alkyl radical or said rings being saturated or not and optionally substituted with at least one substituent A2;  in which: R1, R2, R4 and R5, which are identical or different, are chosen from hydrogen, a halogen, the groups OR7, SR7, NR7R'7, COOR7, CONR7R'7, CF3, CN, NR7COR'7, SO2R7, S02NR7R'7, NR7SO2R'7, COR7, CSR7, OCOR7, COSR7, SCOR7, CSNR7R'7,

 OR, o, SR, o, NR, oR'lo, COOR1o, CH2COORio, CONR10R'10, CF3, CN, NR107COR'10, SO2R, o, SO2NR, oR'lo, NRiSO2R'lo, COR, O, CSR1O, OCOR, O, COSR1O, SCOR, O, CSNR, OR'lo, NR, OCONR ', oR "lo, NR1OC (= NRI1O) NR" 1OR "11O, NR1OCSNR'1OR" 10, NR, OCSR'lo, with Rlo , R'lo, R "10 and R '" 10 identical or different designating hydrogen, a linear or branched C1-C20 alkyl radical or a ring of 4 to 7 atoms, optionally containing at least one heteroatom, isolated or attached to another cycle, the alkyl radical or said rings being saturated or not, as an inhibitor of 15-hydroxyprostaglandin dehydrogenase 5. Use of at least one styryl-pyrazole compound of formula (I) or a salt thereof

 - A1, A2, A3, A4 and A5 being independently selected from halogens, the groups <Desc / Clms Page number 21>  OR, O, SR, o, NR, oR'lo, COOR, O, CH2COOR10, CONR, oR'lo, CF3, CN, NR107COR'10, SO2R, o, SO2NR, oR'lo, NRiOS02R'10, COR, O, CSRiO, OCOR, O, COSRiO, SCOR, G, CSNRlOR '10, NR10CONR'10R "io> NRioC (= NR'io) NR" 1oR' "io, NRIOCSNR'1oR> o NR, OCSR'lo, with R 10, R 10, R 10 and R 10, which may be identical or different, denote hydrogen, a linear or branched C 1 -C 20 alkyl radical or a ring of 4 to 7 atoms, optionally containing at least one heteroatom, isolated or attached to another cycle, the alkyl radical or said rings being saturated or not, for the manufacture of a human hair composition, intended to treat disorders related to 15-hydroxyprostaglandin dehydrogenase.

 another cycle, the alkyl radical or said rings being saturated or not and optionally substituted with at least one substituent A5; - A1, A2, A3, A4 and A5 being independently selected from halogens, the groups 6. Use according to one of the preceding claims, characterized in that at least one of R1 and R2 represent a hydrogen atom or a halogen atom. 7. Use according to one of the preceding claims, characterized in that R1 and R2 are located on the phenyl ring in the ortho position of the branch of the pyrazole part. 8. Use according to one of the preceding claims, characterized in that R1 and R2 represent a halogen atom and in particular a chlorine atom. 9. Use according to one of the preceding claims, characterized in that R3 represents CN. 10. Use according to the preceding claim, characterized in that R4, R5, R6

 represent independently of each other CH2CH2OR10, NH2, H or CN. 11. Use according to one of the preceding claims, characterized in that R6 represents CH2CH20H. 12. Use according to one of the preceding claims, characterized in that R4 represents NH2 or H. 13. Use according to one of the preceding claims, characterized in that R5 represents CN or H. 14. Use according to one of the preceding claims, characterized in that the compound of formula (I) is chosen from: Compound 1

<Desc / Clms Page number 22>  15. Use according to one of the preceding claims, characterized in that the salt of the compound of formula (I) is a salt selected from sodium salts, potassium, zinc salts (Zn2 +), calcium (Ca2 +) , copper (Cu2 +), iron (Fe2 +), strontium (Sr2 +), magnesium (Mg2 +), manganese (Mn2 +), triethanolamine salts, monoethanolamine, diethanolamine, hexadecylamine, N, N, N ', N'tetrakis (2-hydroxypropyl) ethylene di-amine, tris-hydroxymethyl aminomethane, hydroxides and carbonates.

 Compound 5

 Composed 4 f '' \ LJ @

 Compound 3

 Compound 2 <Desc / Clms Page number 23>  16. Use according to one of the preceding claims, characterized in that the compound of formula (I) is used at a concentration ranging from 10-3 to 5%, preferably from 10-2 to 2%, relative to the weight total of the composition. 17. Use according to one of claims 2 to 16, characterized in that the composition is a topically applied composition. 18. A topically applied hair care composition containing a physiologically acceptable medium and an effective amount of at least one styrylpyrazole compound of formula (I) or a salt thereof,

 in which: R1, R2, R4 and R5, which are identical or different, are chosen from hydrogen, a halogen, the groups OR7, SR7, NR7R'7, COOR7, CONR7R'7, CF3, CN, NR7COR'7, SO2R7,

 S02NR7R'7, NR7SO2R'7, COR7, CSR7, OCOR7, COSR7, SCOR7, CSNR7R'7, NR7CONR'7R "7, NR7C (= NR'7) NR" 7R '"7, NR7CSR'7, NR7CSNR'7R" 7, linear or branched, saturated or unsaturated C 1 -C 20 alkyl radicals, saturated or unsaturated rings of 4 to 7 atoms, optionally containing at least one heteroatom, these rings being separable or contiguous, alkyl and the rings may, in addition, be substituted by at least one substituent A1, with R7, R'7, R "7 and R '' '7, independently denoting hydrogen, a linear or branched C1-C20 alkyl radical; or a ring of 4 to 7 atoms, optionally containing at least one heteroatom, isolated or attached to another ring, the alkyl radical or said rings being saturated or not and optionally substituted with at least one substituent A2;

 R3 is chosen from CN, COORB, CONR8R'8, COR8, SOzRs, SO2NR8R'8, with R8 and R'8 independently denoting hydrogen or a linear or branched C1-C20 alkyl radical or a ring of from 4 to 7 atoms, isolated or attached to another ring and optionally containing at least one heteroatom, the alkyl radical or said rings being saturated or not and optionally substituted by at least one substituent A3, - R6 is chosen from hydrogen, the groups COOR9, COR9, CSR9, COSRq,

 CONRgR'g, SO2R9, SO2NRgR'9, linear or branched, saturated or unsaturated C1-C20 alkyl radicals and saturated or unsaturated 4 to 7 atom rings, optionally containing at least one heteroatom, these rings being separable or contiguous, alkyl radicals and rings may, in addition, be substituted by at least one substituent A4, with Rg and R'9 identical or different designating hydrogen, a linear or branched C 1 -C 20 alkyl radical or a ring of 4 to 7 atoms, optionally containing at least one heteroatom, isolated or attached to another ring, the alkyl radical or said rings being saturated or not and optionally substituted with at least one substituent A5; <Desc / Clms Page number 24>  OR, o, SR, o, NR, oR'lo, COOR, O, CH2COORio, CONR, oR'lo, CF3, CN, NR10COR ', o, SO2R, o, SO2NR, oR'lo, NR, OS02R'lo , COR, O, CSR1o, OCORo, COSR1o, SCOR, O, CSNR, oR'lo, NR, oCONR ', oR "lo, NRIOC (= NR'IO) NR", OR "'10, NR1oCSNR'1oR" io , NR, OCSR'lo, with Rlo, R'10, R "and Roo identical or different designating hydrogen, a linear or branched C 1 -C 20 alkyl radical or a ring of 4 to 7 atoms, optionally containing at least one heteroatom, isolated or attached to another ring, the alkyl radical or said rings being saturated or not 19. Composition according to claim 18, characterized in that at least one of R1 and R2 represents a hydrogen atom or a halogen atom.

 - A1, A2, A3, A4 and A5 being independently selected from halogens, the groups 20. Composition according to claim 18 or 19, characterized in that R1 and R2 are located on the phenyl ring, in the ortho position of the branch of the pyrazole part. 21. Composition according to one of claims 18 to 20, characterized in that R1 and R2 represent a halogen atom and in particular a chlorine atom. 22. Composition according to one of claims 18 to 21, characterized in that R3 represents CN. 23. Composition according to one of claims 18 to 22, characterized in that R4,

 R5, R6 are independently of each other CH2CH20R, O, NH2, H or CN 24. Composition according to one of claims 18 to 23, characterized in that R6 represents CH2CH20H. 25. Composition according to one of claims 18 to 24, characterized in that R represents NH2 or H. 26. Composition according to one of claims 18 to 25, characterized in that R5 represents CN or H. 27. Composition according to one of claims 18 to 26, characterized in that the compound of formula (I) is chosen from:

<Desc / Clms Page number 25>

 28. Composition according to one of claims 18 to 27, characterized in that the salt of the compound of formula (I) is a salt selected from sodium, potassium, calcium (Zn 2+), calcium salts ( Ca2 +), copper (Cu2 +), iron (Fe2 +), strontium

 (Sr2 +), magnesium (Mg2 +), manganese (Mn2 +), the salts of tn-ethanolammonoethanolamine, diethanolamine, hexadecylamine, N, N, N ', N'-tetrakis- (hydroxy- <Desc / Clms Page number 26>  propyl-2) ethylene di-amine, tris-hydroxymethyl aminomethane, hydroxides and carbonates. 29. Composition according to one of claims 18 to 28, characterized in that the compound of formula (I) is used at a concentration ranging from 10-3 to 5%, preferably from 10-2 to 2%, relative to to the total weight of the composition. 30. Composition according to one of claims 18 to 29, characterized in that it is in the form of hair cream or lotion, shampoo or after shampoo. 31. Composition according to one of claims 18 to 30, characterized in that it is in the form of aqueous solution or suspension, alcoholic or hydro-alcoholic. 32. Composition according to one of claims 18 to 31, characterized in that it contains other ingredients chosen from solvents, thickeners or gelling agents of aqueous phase or oily phase, the dyestuffs soluble in the medium of the composition, fillers, pigments, antioxidants, preservatives, perfumes, electrolytes, neutralizers, UV blocking agents, cosmetic and pharmaceutical active agents, and mixtures thereof. 33. Composition according to one of claims 19 to 32, characterized in that it contains additional compounds promoting regrowth and / or limiting hair loss such as aminexil, 6-0 - [(9Z, 12Z) octahydromycin, lipoxygenase inhibitors, bradykinin inhibitors, prostaglandins and their derivatives, prostaglandin receptor agonists or antagonists, non-prostanoid prostaglandin analogues, vasodilators, antiandrogens, cyclosporins and their analogues, antimicrobials, anti-inflammatories, retinoids, benzalkonium chloride, benzethonium chloride, phenol, # stradiol, chlorpheniramine maleate, chlorophyllin derivatives, cholesterol, cysteine, methionine, menthol, peppermint oil, calcium panthotenate, panthenol, resorcinol, protein kinase C activators, glycosidase inhibitors, Glycosaminoglycanase inhibitors, pyroglutamic acid esters, hexosaccharide or acyl hexosaccharic acids, substituted aryl ethenyls, N-acyl amino acids, flavonoids, ascomycin derivatives and analogues, histamine antagonists, saponins , proteoglycanase inhibitors, estrogen agonists and antagonists, pseudoterines, cytokines and promoters of growth factors, IL-1 or IL-6 inhibitors, IL-10 promoters, TNF inhibitors, vitamins, hydroxy acids, benzophenones, hydantoin, octopirox, retinoic acid; antipruritic agents, antiparasitics, antifungals, nicotinic acid esters, calcium antagonists, hormones, triterpenes, antiandrogens, steroidal or nonsteroidal 5-a-reductase inhibitors, channel agonists potassium, their mixtures. 34. Composition according to one of Claims 19 to 33, characterized in that it contains, in addition, another active agent chosen from proteins, protein hydrolysates, amino acids, polyols, urea, allantoin, sugars and sugar derivatives, plant extracts, hydroxy acids, retinol or tocopherol derivatives, essential fatty acids, ceramides, essential oils, salicylic acid and its derivatives such as n-octanoyl Salicylic acid, esters of hydroxy acids, phospholipids. <Desc / Clms Page number 27>  35. Process for the cosmetic treatment of the hair and / or the scalp, characterized in that it consists in applying to the hair and / or the scalp, a cosmetic composition as defined in any one of claims 18 to 34, to leave it in contact with the hair and / or the scalp, and possibly to rinse.