2-amino-1,3-alkanediol compositions for inducing/stimulating hair growth and/or retarding hair loss

Topically applicable hair growth-/hair loss-affecting cosmetic/pharmaceutical compositions for treating mammalian subjects with hair or scalp disorders, comprise an effective amount of at least one 2-amino-1,3-alkanediol compound having the structural formula (I): ##STR1## formulated into a physiologically topically acceptable carrier medium therefor.

BACKGROUND OF THE INVENTION
 1. Technical Field of the Invention
 The present invention relates to novel cosmetic and/or pharmaceutical
 compositions for topical application to the hair and/or scalp of mammalian
 subjects, comprising an effective amount of at least one
 2-amino-1,3-alkanediol, or derivative thereof, and to the use of such
 novel compositions for inducing and/or stimulating hair growth and/or
 retarding hair loss.
 2. Description of the Prior Art
 In human subjects, hair growth and its renewal are principally determined
 by the activity of the hair follicles. This activity is cyclical and
 essentially entails three phases, namely, the anagenic phase, the
 catagenic phase and the telogenic phase.
 The active anagenic phase, or growth phase, which lasts for several years
 and during which the hair grows longer, is followed by a very short and
 transitory catagenic phase, which lasts a few weeks, and then by a resting
 or quiescent phase, designated the telogenic phase, which lasts a few
 months.
 At the end of the rest period, the hair falls out and another cycle begins
 anew. The head of hair is thus constantly renewed and, of the
 approximately 150,000 hairs on a human head, at any given instant
 approximately 10% are at rest and will therefore be replaced in a few
 months.
 In a significant number of cases, early hair loss occurs in genetically
 predisposed subjects and it affects men in particular. It is more
 particularly androgenetic or androgenic alopecia or, alternatively,
 androgeno-genetic alopecia.
 This alopecia is essentially due to a disturbance in hair renewal which
 results, at first, in an acceleration in the frequency of the cycles at
 the expense of the quality of the hair and then of its amount. A
 progressive thinning of the head of hair occurs by regression of the
 so-called "terminal" hairs to the downy stage. Certain regions are
 preferentially affected, in particular the temple or frontal areas in men
 and, in women, a diffuse alopecia of the vertex is observed.
 Compositions that eliminate or reduce the effects of alopecia and, in
 particular, that induce or stimulate hair growth or decrease hair loss
 have long been considered desiderata in the cosmetic and pharmaceutical
 industries.
 In this regard, a large number of very diverse active compounds or
 substances have already been suggested for such purposes, for example
 vitamins, such as vitamin E, amino acids, such as serine or methionine,
 vasodilators, such as acetylcholine and derivatives thereof, female
 hormones, such as estradiol, keratolytic agents, such as salicylic acid,
 or chemical compounds, such as 2,4-diamino-6-piperidinopyrimidine 3-oxide
 or "Minoxidil," described in U.S. Pat. No. 4,596,812 or, alternatively,
 its many derivatives, such as those described in EP-353,123, EP-356,271,
 EP-408,442, EP-522,964, EP-420,707, EP-459,890 and EP-519,819.
 Also exemplary thereof are
 6-amino-1,2-dihydro-1-hydroxy-2-imino-4-piperidinopyrimidine and
 derivatives thereof, which are described, more particularly, in U.S. Pat.
 No. 4,139,619.
 Nonetheless, considerable research and development is continuing in this
 art in quest of yet other such valuable active agents.
 Minoxidil, while it remains the reference compound in the field, exhibits
 not insignificant side effects which complicate the use thereof.
 SUMMARY OF THE INVENTION
 Accordingly, a major object of the present invention is the provision of
 compounds of the 2-amino-1,3-alkanediol type for efficaciously
 inducing/stimulating hair growth and/or decreasing hair loss, without
 exhibiting the disadvantages and drawbacks to date characterizing the
 state of this art.
 DETAILED DESCRIPTION OF BEST MODE AND SPECIFIC/PREFERRED EMBODIMENTS OF THE
 INVENTION
 More particularly according to the present invention, the
 2-amino-1,3-alkanediol type compounds or derivatives thereof constitute
 active agents emanating from tissues which are known to the art by the
 very general term of "sphingolipids."
 Among these sphingolipids, N-acylated derivatives based on sphinganine
 [(2S,3R)-2-amino-1,3-octadecanediol] are ceramides mostly present in the
 hair, whereas the analogous derivatives based on sphingenine
 [(2S,3R,4E)-2-amino-4-octadecene-1,3-diol), other ceramides, constitute a
 fraction of the lipids mostly present in the stratum corneum of the skin.
 The ceramides are formulated into cosmetics in the natural or synthetic
 state, for example, to reinforce the barrier effect of the stratum corneum
 in order to reduce water loss and thus dryness of the skin (GB-2,178,312,
 GE-2,213,723, EP-227,994, EP-282,616 and EP-556,957).
 They are also formulated into cosmetic compositions for their properties
 which confer a better elasticity on the skin (EP-500,437) or into
 compositions for hair use in order to reinforce the hair and/or to repair
 the damage caused by the continual attacks to which the latter is
 subjected.
 Hitherto, to the knowledge of the assignee hereof, it has never been
 described nor even suggested that 2-amino-1,3-alkanediols or derivatives
 thereof exert an effect or influence on cell proliferation and still less
 on keratinocyte proliferation.
 It is on the basis of this new property of these aminodiols that it has
 unexpectedly been shown that these compounds also exert an effect on the
 survival of the hair follicle.
 Thus, by increasing the survival time of the hair follicle, the anagenic
 phase of the hair cycle is lengthened, which has the effect of delaying
 hair loss.
 Among the sphingolipids, compounds based on sphingenine induce apoptosis,
 directly or through a series of events involving cellular proteins. This
 phenomenon, which results in cell death, transposed to the hair cycle,
 elicits a halt in the growth of the follicle and in hair loss.
 The synthesis of compounds based on sphingenine results from several
 distinct mechanisms. Exemplary are the activation of cellular
 sphingomyelinase by .alpha.-type tumor necrosis factor (TNF-.alpha.), by
 vitamin D, by interleukin-1, by the FAS antigen or ionizing radiation. It
 is also known that compounds based on sphingenine can also be generated by
 activation of acyl-CoA: sphinganine (sphingosine) N-acyltransferase (EC
 2.3.1.24).
 Thus, it has now unexpectedly been determined that the compounds of formula
 (I) can interfere both during the synthesis of the compounds based on
 sphingenine and during the events induced by these compounds. The
 consequence of this is to prevent the apoptosis induced by the compounds
 based on sphingenine and also to stimulate cell growth and viability.
 In chemotherapeutic anticancer treatments, the use of anticancer agents
 causes cell death in the hair follicle, resulting in hair loss. This
 induced alopecia is generally transitory, but can sometimes be permanent
 (A. M. Hussein, South Med. J., 1993, 86, 489-496). This side effect causes
 some patients to refuse this type of therapy (K. O. Baxley et al., Cancer
 Nurs., 1984, 7, 499-503).
 Doxorubicin, for example, induces such a hair loss. It is known that
 doxorubicin activates ceramide synthase, an enzyme whose activation
 results in an increase in the intracellular level of compounds based on
 sphingenine which themselves induce the phenomenon of apoptosis and of
 cell death.
 It has now been determined that the compounds of formula (I) below
 counteract the harmful side effects of anticancer agents, such as, for
 example, doxorubicin, by increasing the cell viability of the
 keratinocytes of the hair follicles.
 The present invention features the formulation, into
 cosmetic/pharmaceutical compositions, as active agents promoting hair
 survival and/or growth, of at least one compound having the general
 formula (I):
 ##STR2##
 in which R.sub.1 is a saturated or unsaturated, optionally hydroxylated,
 linear or branched hydrocarbon radical having from 4 to 28 carbon atoms;
 R.sub.2 is a hydrogen atom or the radical:
 ##STR3##
 wherein R.sub.3 is a saturated or unsaturated, optionally hydroxylated,
 linear or branched hydrocarbon radical having from 1 to 29 carbon atoms,
 with the proviso that the hydroxyl group thereof may be esterified by a
 saturated or unsaturated, linear or branched acyl radical having from 2 to
 30 carbon atoms; and X is a hydrogen atom or the OH radical, or of at
 least one of its optical isomers or one of the diastereoisomers.
 R.sub.1 preferably has from 11 to 23 carbon atoms and even more preferably
 14 carbon atoms.
 R.sub.2 preferably is the radical:
 ##STR4##
 wherein R.sub.3 preferably has from 7 to 25 carbon atoms.
 R.sub.1 is preferably a saturated and/or linear hydrocarbon radical, more
 particularly a saturated linear hydrocarbon radical.
 R.sub.1 is more preferably a saturated hydrocarbon radical having 14 carbon
 atoms and even more preferably R.sub.1 is a saturated linear hydrocarbon
 radical having 14 carbon atoms.
 The active agent promoting hair survival and/or growth can be a mixture of
 compounds of formula (I) for which R.sub.1 and/or R.sub.2 are radicals of
 different chain lengths.
 These compounds can be employed in the form of a pure isomer or of a
 mixture of isomers.
 These compounds present the advantage of not inducing undesirable side
 effects, which makes their use without risk for the user.
 Exemplary compounds of formula (I) include:
 2-Amino-1,3-octadecanediol;
 2-Acetylamino-1,3-octadecanediol;
 2-Octanoylamino-1,3-octadecanediol;
 2-Tetracosanoylamino-1,3-octadecanediol;
 2-N-(2-Hydroxyhexadecanoyl)amino-1,3-octadecanediol;
 2-Oleoylamino-1,3-octadecanediol;
 2-Hexadecanoylamino-1,3-octadecanediol;
 2-N-(2-Hydroxydocosanoyl)amino-1,3-octadecanediol;
 2-Amino-1,3,4-octadecanetriol;
 2-Hexadecanoylamino-1,3,4-octadecanetriol; and
 2-N-(2-Hydroxyhexadecanoyl)amino-1,3,4-octadecanetriol.
 In a preferred embodiment according to the invention,
 2-N-(2-hydroxyhexadecanoyl)amino-1,3-octadecanediol and
 2-oleoylamino-1,3-octadecanediol are employed.
 The amount of the compounds of formula (I) which are advantageously used
 according to the invention depends, of course, on the nature of the
 compound itself, on its physicochemical properties and on the technique
 for the application thereof. One skilled in this art is cognizant how to
 adjust the amount of the at least one compound of formula (I) according to
 the requirements thereof.
 For example, the compounds of formula (I) can be formulated at
 concentrations by weight of from 10.sup.-4 % to 20% and preferably from
 10.sup.-3 % to 10% in the composition.
 The present invention also features the use of at least one compound of
 formula (I) for combating an alopecia induced by an anticancer treatment
 entailing chemotherapy.
 When the compound of formula (I) is formulated into a composition which
 must be topically applied onto the skin and particularly onto the scalp,
 this composition can be provided in all of the pharmaceutical dosage forms
 typically employed.
 For topical application onto the skin, the composition can be in the form,
 in particular, of an aqueous, alcoholic, aqueous/alcoholic or oily
 solution, or of a dispersion of the lotion or serum type, of an emulsion
 having a liquid or semi-liquid consistency of the milk type, obtained by
 dispersion of a fatty phase in an aqueous phase (O/W) or vice versa (W/O),
 or of a suspension or of an emulsion with a soft consistency of the
 aqueous or anhydrous gel, foam or cream type, or, alternatively, of
 microcapsules or microparticles, or of a vesicular dispersion of ionic
 and/or nonionic type. It can also be in the form of an aerosol composition
 also comprising a pressurized propellent agent.
 Whatever its form, this composition is formulated according to the usual
 techniques.
 The amounts of the different constituents of the compositions according to
 the invention are those that are conventional in the fields under
 consideration.
 The compounds according to the invention can also be formulated into
 various compositions for hair care and, in particular, shampoos,
 hair-setting lotions, treating lotions, styling creams or gels, dye
 compositions (in particular oxidation dyes), optionally in the form of
 color-enhancing shampoos, hair-restructuring lotions, permanent-wave
 compositions (in particular compositions for the first step of a permanent
 wave), shampoos for combating parasites, and the like.
 When the subject composition comprises an emulsion, the proportion of the
 fatty phase advantageously ranges from 5% to 80% by weight, and preferably
 from 5% to 50% by weight, with respect to the total weight of the
 composition. The oils, the waxes, the emulsifiers and the coemulsifiers
 comprising the composition in the emulsion form are selected from among
 those conventionally used in the cosmetics field. The emulsifier and the
 coemulsifier are present, in the composition, in a proportion
 advantageously ranging from 0.3% to 30% by weight, and preferably from
 0.5% to 20% by weight, with respect to the total weight of the
 composition. The emulsion can, in addition, contain lipid vesicles.
 When the composition is an oily gel or solution, the fatty phase can
 constitute more than 90% of the total weight of the composition.
 Also intended are compositions comprising at least one compound of formula
 (I) as an active principle intended to induce and/or to stimulate hair
 growth and/or to slow down or retard its loss comprising liposomed form,
 such as, in particular, described in WO-94/22468, filed Oct. 13, 1994 and
 assigned to Anti-Cancer Inc. The compound encapsulated in the liposomes
 can thus be delivered selectively to the hair follicle.
 The subject compositions can also contain additives and adjuvants which are
 conventional in the cosmetics field, such as hydrophilic or lipophilic
 gelling agents, hydrophilic or lipophilic additives, preservatives,
 antioxidants, solvents, fragrances, fillers, screening agents, odor
 absorbers and colorants. The amounts of these different additives and
 adjuvants are those typically employed in the cosmetics field and range,
 for example, from 0.01% to 10% of the total weight of the composition.
 These additives and adjuvants, depending on the nature thereof, can be
 introduced into the fatty phase, into the aqueous phase and/or into the
 lipid spherules.
 Exemplary oils or waxes according to the invention include mineral oils
 (liquid petrolatum), vegetable oils (liquid fraction of karite butter,
 sunflower oil), animal oils (perhydrosqualene), synthetic oils (purcellin
 oil), silicone oils or waxes (cyclomethicone) and fluorinated oils
 (perfluoropolyethers), beeswax, carnauba wax or paraffin wax. Fatty
 alcohols and fatty acids (stearic acid) can be added to these oils.
 Exemplary emulsifiers which are suitable per the invention include glyceryl
 stearate, polysorbate 60 and the PEG-6/PEG-32/glycol stearate mixture
 marketed under the trademark Tefose.RTM.63 by Gattefosse.
 Exemplary solvents according to the invention include the lower alcohols,
 in particular ethanol and isopropanol, or propylene glycol.
 And exemplary hydrophilic gelling agents include carboxyvinyl polymers
 (carbomer), acrylic copolymers such as acrylate/alkyl acrylate copolymers,
 polyacrylamides, polysaccharides such as hydroxypropylcellulose, natural
 gums and clays and representative lipophilic gelling agents include the
 modified clays such as bentones, metal salts of fatty acids such as
 aluminum stearates, and hydrophobic silica, ethylcellulose or
 polyethylene.
 The subject compositions can also contain other hydrophilic active
 principles, such as proteins or protein hydrolysates, amino acids,
 polyols, urea, allantoin, sugars and sugar derivatives, water-soluble
 vitamins, plant extracts and hydroxy acids.
 Exemplary such lipophilic active principles include those of retinol
 (vitamin A) and derivatives thereof, tocopherol (vitamin E) and
 derivatives thereof, essential fatty acids, ceramides other than the
 compounds of formula (I), essential oils or salicylic acid and derivatives
 thereof.
 It is also envisaged to formulate, in combination with the compounds of
 formula (I), compounds which further improve the activity with respect to
 hair regrowth and/or with respect to slowing down or retarding hair loss
 and which are already known to this art for such activity.
 Exemplary such compounds include, without limitation:
 (a) nicotinic acid esters, including in particular tocopherol nicotinate,
 benzyl nicotinate and C.sub.1 -C.sub.6 alkyl nicotinates, such as methyl
 nicotinate or hexyl nicotinate;
 (b) pyrimidine derivatives, such as 2,4-diamino-6-piperidinopyrimidine
 3-oxide or "Minoxidil," described in U.S. Pat. No. 4,596,812 or,
 alternatively, its many derivatives, or compounds such as
 6-amino-1,2-dihydro-1-hydroxy-2-imino-4-piperidinopyrimidine and
 derivatives thereof, as described in U.S. Pat. No. 4,139,619;
 (c) agents promoting hair regrowth, such as those described in published
 European patent application No. 0,648,488 assigned to the assignee hereof;
 (d) antibacterial agents, such as macrolides, pyranosides and
 tetracyclines, and in particular erythromycin;
 (e) calcium antagonists, such as cinnarizine and diltiazem;
 (f) hormones, such as estriol or analogs thereof, or thyroxine and its
 salts;
 (g) steroidal anti-inflammatory agents, such as corticosteroids (for
 example hydrocortisone);
 (h) antiandrogen agents, such as oxendolone, spironolactone or
 diethylstilbestrol;
 (i) 5-.alpha.-reductase antagonists;
 (j) OH-radical scavengers, such as dimethyl sulfoxide.
 Other such compounds include, for example, diazoxide, spiroxazone,
 phospholipids, such as lecithin, linoleic and linolenic acids, salicylic
 acid and derivatives described in FR-2,581,542, such as the derivatives of
 salicylic acid bearing an alkanoyl substituent having from 2 to 12 carbon
 atoms in the 5 position of the benzene ring, hydroxycarboxylic or
 ketocarboxylic acids and esters thereof, lactones and their corresponding
 salts, anthralin, carotenoids, eicosatetraenoic and eicosatrienoic acids
 or the esters and amides thereof, or vitamin D and derivatives thereof.
 According to the invention, it is possible, inter alia, to combine at least
 one compound of formula (I) with other active agents intended, in
 particular, for the prevention and/or the treatment of cutaneous
 conditions, particularly conditions of the scalp. Exemplary of such active
 agents are:
 (1) agents which modulate cutaneous pigmentation and/or proliferation
 and/or differentiation, such as retinoic acid and its isomers, retinol and
 its esters, vitamin D and its derivatives, estrogens, such as estradiol,
 kojic acid or hydroquinone;
 (2) antibacterials, such as clindamycin phosphate, erythromycin or
 antibiotics from the tetracycline class;
 (3) agents for combating parasites, in particular metronidazole, crotamiton
 or pyrethroids;
 (4) antifungals, in particular compounds belonging to the imidazole class,
 such as econazole, ketoconazole or miconazole or their salts, polyene
 compounds, such as amphotericin B, compounds of the allylamine family,
 such as terbinafine, or alternatively octopirox;
 (5) antiviral agents, such as acyclovir;
 (6) steroidal anti-inflammatory agents, such as hydrocortisone,
 betamethasone valerate or clobetasol propionate, or nonsteroidal
 anti-inflammatory agents, such as ibuprofen and its salts, diclofenac and
 its salts, acetylsalicylic acid, acetaminophen or glycyrrhetinic acid;
 (7) anaesthetic agents, such as lidocaine hydrochloride and derivatives
 thereof;
 (8) antipruriginous agents, such as thenaldine, trimeprazine or
 cyproheptadine;
 (9) keratolytic agents, such as .alpha.- and .beta.-hydroxycarboxylic acids
 or .beta.-ketocarboxylic acids, their salts, amides or esters and more
 particularly hydroxy acids, such as glycolic acid, lactic acid, salicylic
 acid, citric acid and, generally, fruit acids, and 5-(n-octanoyl)salicylic
 acid;
 (10) agents for combating free radicals, such as .alpha.-tocopherol or its
 esters, superoxide dismutases, certain metal chelating agents or ascorbic
 acid and its esters;
 (11) antiseborrhoeics, such as progesterone;
 (12) antidandruff agents, such as octopirox or zinc pyrithione;
 (13) antiacne agents, such as retinoic acid or benzoyl peroxide;
 (14) substances such as substance P, CGRP or bradykinin antagonists or NO
 synthase inhibitors, which compounds are described as being active for the
 treatment of sensitive skins and as exhibiting antiirritant effects, in
 particular with respect to irritant compounds possibly present in the
 compositions.
 Thus, this invention also features compositions comprising an effective
 amount of at least one compound of formula (I) and at least one active
 agent selected from among antibacterial agents, agents for combating
 parasites, antifungal agents, antiviral agents, anti-inflammatory agents,
 antipruriginous agents, anaesthetic agents, keratolytic agents, agents for
 combating free radicals, antiseborrhoeic agents, antidandruff agents,
 antiacne agents, agents which modulate cutaneous pigmentation and/or
 proliferation and/or differentiation, substance P, CGRP (calcitonin gene
 related peptide) or bradykinin antagonists or NO synthase inhibitors.
 In the compositions according to the invention, the substance P, CGRP or
 bradykinin antagonist or the NO synthase inhibitor is preferably
 incorporated in an amount ranging from 0.000001% to 20% of the total
 weight of the composition and in particular in an amount constituting from
 0.0001% to 15% of the total weight of the composition.
 It is envisaged to employ at least one of the compounds corresponding to
 the formula (I) for the formulation of a pharmaceutical, particularly
 dermatological, composition intended to treat hair loss and/or to promote
 hair regrowth.
 In general, these pharmaceutical compositions are distinguished, in
 particular, from cosmetic compositions by the amount of active principle
 which they contain. One skilled in this art can readily determine the
 amount of active principle which can be used as a function of the result
 desired, but also taking account of the mode of administration envisaged.
 For example, the compound of formula (I) can be employed for the
 preparation of a pharmaceutical composition at a concentration of from
 0.01% to 20% and preferably from 0.1% to 10% by weight with respect to the
 weight of the composition.
 The cosmetic or pharmaceutical compositions according to the invention can
 be topically applied onto the alopecic areas of the scalp and hair of an
 individual and optionally maintained in contact for a number of hours and
 optionally rinsed. It is possible, for example, to apply the composition
 containing an effective amount of at least one compound of formula (I) in
 the evening, to retain the composition in contact overnight and optionally
 to shampoo in the morning. These applications can be repeated daily for
 one or a number of months, depending on the particular individuals
 involved.
 Thus, the present invention also features a regimen for the cosmetic
 treatment of the hair and/or of the scalp, comprising topically applying
 onto the hair and/or the scalp, a cosmetic composition comprising an
 effective amount of at least one compound of formula (I) in a
 physiologically topically acceptable carrier medium therefor, maintaining
 this composition in contact with the hair and/or the scalp, and optionally
 later rinsing the same therefrom.
 In order to further illustrate the present invention and the advantages
 thereof, the following specific examples are given, it being understood
 that same are intended only as illustrative and in nowise limitative.

In said examples to follow, all parts and percentages are given by weight,
 unless otherwise indicated.
 EXAMPLE 1
 Measurement of the Proliferative Influence of 2-amino-1,3-octadecanediol
 and Derivatives Thereof on Cultured Keratinocytes
 HaCat cells (Boukamp and coworkers, J. Cell Biol., vol. 106, March 1988,
 761-771) were cultured in DMEM medium (marketed by Gibco) containing amino
 acids (mixture of nonessential amino acids) at a concentration of 0.1 mM,
 penicillin and streptomycin at respective concentrations of 50
 International Units per millimeter and of 50 .mu.g/ml, glutamine at a
 concentration of 2 mM, sodium pyruvate at a concentration of 1 mM and 10%
 fetal calf serum. These cells were inoculated at a density of 10,000 cells
 per well in the 24 wells of plates of the multiwell type (Costar, France).
 24 hours after inoculation, the cells were contacted with the various test
 compounds in a KBM medium (marketed by Clonetics) containing 0.15 mM of
 calcium ion, insulin at 5 .mu.g/ml, hydrocortisone at 0.5 .mu.g/ml and
 lipid-free bovine serum albumin at 1 .mu.g/ml.
 Cellular counting was carried out 5 days after the addition of the various
 ceramides using a cell counter of the Coulter Counter type.
 The various compounds were tested at 0.5 nM, 5 nM, 50 nM and 500 nM.
 The results, expressed as percentage, represent the increase in the number
 of cells with respect to the control, namely, with respect to a culture
 produced under the same conditions in the absence of sphinganine.
 The different compounds tested were:
 A: 2-amino-1,3-octadecanediol,
 B: 2-oleoylamino-1,3-octadecanediol,
 C: 2-N-(2-hydroxyhexadecanoyl)amino-1,3- octadecanediol,
 D: 2-tetracosanoylamino-1,3-octadecanediol,
 E: 2-acetylamino-1,3-octadecanediol,
 F: 2-octanoylamino-1,3-octadecanediol.

Control 0
 A +17
 B +23
 C +20
 C16H -25
 The results evidence that 2-amino-1,3-octadecanediol (A),
 2-oleoylamino-1,3-octadecanediol (B) and
 2-N-(2-hydroxyhexadecanoyl)amino-1,3-octadecanediol (C) increased the
 viability of the cultured keratinocytes, whereas N-palmitoylsphingenine
 (C16H) elicited a cytotoxic effect on the cultured cells.
 This result indicates that compounds based on sphingenine cannot be used
 for the treatment of hair follicles since they cause cell death in
 culture.
 EXAMPLE 3
 Measurement of the Effect of 2-amino-1,3-octadecanediol and Derivatives
 Thereof on the Cell Cycle
 HaCat cells were cultured as above.
 These were then inoculated at a density of 20,000 cells per well in the 24
 wells of plates of the multiwell type (Costar, France).
 24 hours after inoculation, the cells were contacted with the various test
 compounds in a KBM medium (marketed by Clonetics) containing insulin at 5
 .mu.g/ml and hydrocortisone at 0.5 .mu.g/ml and 5-bromo-2'-deoxyuridine
 (BrdU) at 1 .mu.M.
 The phase of the cell cycle was evaluated 48 hours later by measuring the
 incorporation of BrdU in genomic deoxyribonucleic acid. This was carried
 out using a BrdU fast kit, marketed by Boehringer, according to the
 supplier's instructions.
 The compounds A, B and C of the above example were tested at a
 concentration of 50 nM.
 The results, expressed as percentage, represent the increase in the number
 of cells which have entered into the S phase with respect to the control,
 namely, with respect to a culture produced under the same conditions in
 the absence of alkanediol compounds.

72 hours 96 hours
 Control 0 0
 A 36 41
 B 43 51
 C 17 43
 The results evidence that 2-amino-1,3-octadecanediol (A),
 2-oleoylamino-1,3-octadecanediol (B) and
 2-N-(2-hydroxyhexadecanoyl)amino-1,3-octadecanediol (C) increase the
 number of keratinocytes which have entered into the S phase, thus
 indicating stimulation of cell mitotic activity.
 EXAMPLE 4
 Measurement of the Effect of 2-amino-1,3-octadecanediol and Derivatives
 Thereof on the Survival of the Hair Follicle in Vitro
 Viable in vitro hair follicles were prepared according to the technique
 described in FR-95/08,465, filed Jul. 12, 1995 and assigned to the
 assignee hereof.
 From a scalp biopsy, a rather fine strip of scalp was isolated using a
 scalpel. The adipose tissue surrounding the follicles was removed with
 microforceps while avoiding damage to the hair bulb. The follicle was cut
 and removed with a scalpel under a microscope in order to separate it from
 its epidermal and dermal surroundings.
 The fragment obtained was maintained in culture in Williams E medium, at
 37.degree. C., in a humid atmosphere in the presence of CO.sub.2.
 The survival of the follicles was evaluated each day by counting the living
 follicles, according to their morphological appearance.
 The results are reported as percentage of surviving follicles per day.
 The experiment was carried out employing the following compounds at a
 concentration of 50 nM:
 B: 2-amino-1,3-octadecanediol,
 C: 2-oleoylamino-1,3-octadecanediol,
 D: 2-N-(2-hydroxyhexadecanoyl)amino-1,3-octadecanediol,
 in comparison with the culture medium without alkanediol (A).

A 0
 B -20
 C +25
 D +28
 E +23
 Doxorubicin caused a decrease in cell viability. The presence in the
 culture medium of a 2-amino-1,3-octadecanediol inhibited this effect and
 increased cell viability.
 EXAMPLE 6
 Effect of 2-amino-1,3-octadecanediol and Derivatives Thereof on Cell
 Viability in the Presence of a Compound Based on Sphingenine,
 N-acetylsphingenine
 The cells were cultured as in Example 5. N-Acetylsphingenine was at a
 concentration of 10 .mu.M.
 The experiment was carried out with the following compounds at a
 concentration of 50 nM:
 C: 2-amino-1,3-octadecanediol,
 D: 2-oleoylamino-1,3-octadecanediol,
 E: 2-N-(2-hydroxyhexadecanoyl)amino-1,3-octadecanediol,
 in comparison with the culture medium without alkanediol and without
 N-acetylsphingenine (A) and with a medium containing only
 N-acetylsphingenine (B).
 The results, expressed as percentage, represent the number of cells with
 respect to the control (A), namely, with respect to a culture produced
 under the same conditions in the absence of alkanediol compounds and of
 N-acetylsphingenine.

A 100
 B 57
 C 72
 D 76
 E 78
 N-Acetylsphingenine caused a decrease in cell viability. The presence in
 the culture medium of a 2-amino-1,3-octadecanediol tended to counteract
 this effect.
 EXAMPLE 7
 This example sets forth specific compositions for topical application to
 the hair and/or the scalp and can be prepared by simple mixing (A.M.:
 Active material):