Hair loss abstract
Composition for slowing down hair loss and inducing and stimulating
its growth, comprising a compound of the following formula: ##STR1##
wherein R.sub.1 and R.sub.3 denote H; R.sub.2 and R.sub.4 denote
H or an alkyl; R.sub.5 denotes H, an alkyl, an alkenyl, a cycloalkyl,
an aryl, an arylalkyl, a hydroxyalkyl or an aminoalkyl; X denotes
H, halogen, alkyl, nitro, benzoyloxy or --NHR.sub.6 where R.sub.6
denotes H, acyl or alkyl; Z denotes sulfur or oxygen, with the proviso
that Z denotes sulfur when X denotes H or R.sub.5 denotes aryl;
Y denotes oxygen or OSO.sub.3 ; as well as its physiologically acceptable
salts.
Hair loss claims
We claim:
1. A composition for slowing down hair loss and for inducing and
stimulating its growth, which comprises, in a physiologically acceptable
medium, between 0.1 and 10% by weight relative to the total weight
of the composition of at least one compound corresponding to the
following formula: ##STR42## in which: R.sub.1 and R.sub.3 denote
a hydrogen atom;
R.sub.2 and R.sub.4, which are identical or different, represent
a hydrogen atom or a C.sub.1 -C.sub.4 alkyl group;
R.sub.5 denotes a hydrogen atom, a C.sub.1 -C.sub.12 alkyl radical,
a C.sub.3 -C.sub.12 alkenyl radical, a C.sub.3 -C.sub.8 cycloalkyl
radical, an aryl radical, an arylalkyl radical or a hydroxyalkyl
or aminoalkyl radical in which the alkyl radical has 1 to 6 carbon
atoms;
X denotes a hydrogen atom, a halogen atom, a C.sub.1 -C.sub.6 alkyl
radical, a nitro group, a benzoyloxy group or a group --NHR.sub.6
in which R.sub.6 denotes a hydrogen atom, an acyl radical or a C.sub.1
-C.sub.6 alkyl radical;
Z denotes sulfur or oxygen, with the proviso that Z denotes sulfur
when X denotes hydrogen or when R.sub.5 denotes an aryl radical;
Y denotes oxygen or OSO.sub.3 ; as well as its addition salts with
physiologically acceptable acids.
2. The composition as claimed in claim 1, wherein, in formula (I),
the C.sub.1 -C.sub.6 alkyl radicals are methyl, ethyl, propyl, n-butyl,
n-pentyl or n-hexyl; the C.sub.1 -C.sub.12 alkyl radicals are methyl,
ethyl, propyl, n-butyl, n-pentyl, n-hexyl, 2-ethylhexyl, octyl,
decyl or are dodecyl; the C.sub.3 -C.sub.12 alkenyl groups are allyl,
butenyl, hexenyl, decenyl or dodecenyl; the aryl radicals are phenyl
or benzyl; and the halogen atoms are chlorine, bromine, fluorine
or iodine.
3. The composition as claimed in claim 1, wherein in the compound
of formula (I) Z denotes sulfur; X denotes chlorine or nitro; R.sub.1,
R.sub.2, R.sub.3 and R.sub.4 denote hydrogen and R.sub.5 denotes
methyl, ethyl, n-butyl, phenyl, 2-hydroxyethyl or 2-aminoethyl.
4. The composition as claimed in claim 1, wherein the compound
of formula (I) is 2,4-diamino-5-chloro-6-n-butyloxypyrimidine 3-oxide
or 2,4-diamino-5-nitro- 6 -n-butyloxypyrimidine 3 -oxide.
5. The pharmaceutical or cosmetic composition, intended to be used
in topical application, which comprises, in a physiologically acceptable
medium, at least one compound as defined in claim 1.
6. The composition as claimed in claim 5, in the form of an anhydrous
or aqueous, ointment, tincture, cream, pomade, powder, patch, impregnated
pad, solution, emulsion, vesicular dispersion, lotion, gel, spray
or suspension.
7. The composition defined in claim 5, in the form of a lotion,
gel, soap, shampoo, aerosol or foam, at a concentration of between
0.01 and 5% by weight.
8. The composition as claimed in claim 5, further comprising antiseborrheic
agents.
9. The composition as claimed in claim 5, further comprising agents
for further improving the activity of the compounds of formula (I)
for slowing down hair loss and for inducing and stimulating its
growth.
10. The composition as claimed in claim 9, wherein the agents are
nicotinic acid esters, steroidal or nonsteroidal antiinflammatory
agents, retinoids, antibacterial agents, calcium antagonistic agents,
hormones, antiandrogenic agents or hydroxyl radical scavengers.
11. The composition as claimed in claim 9, further comprising diazoxide,
spiroxasone, the phospholipids, linoleic or linolenic acids, salicylic
acid or its derivatives, the hydroxycarboxylic or ketocarboxylic
acids, their esters, the lactones their corresponding salts, anthralin,
the carotenoids, 5,8,11,14-eicosatetraynoic or 5,8,11-eicosatriynoic
acids, their esters or amides.
12. The composition as claimed in claim 5, further comprising nonionic
or amphoteric surface-active agents.
13. The composition as claimed in claim 5, wherein the physiologically
acceptable medium consists of water, a mixture of water and one
or more organic solvent(s) or of a mixture of organic solvents,
the organic solvents being pharmaceutically or cosmetically acceptable.
14. The composition as claimed in claim 13, wherein the solvents
are C.sub.1 -C.sub.4 lower alcohols, alkylene glycols or mono- and
dialkylene glycol alkyl ethers.
15. The composition as claimed in claim 5, wherein the physiologically
acceptable medium is thickened by means of thickening and/or gelling
agents and contains preserving agents, stabilizing agents, pH regulating
agents, agents for modifying osmotic pressure, emulsifying agents,
UV-A or UV-B filters or antioxidant agents.
16. Compounds of formula: ##STR43## in which: R.sub.1 and R.sub.3
denote a hydrogen atom;
R.sub.2 and R.sub.4, which are identical or different, represent
a hydrogen atom or a C.sub.1 -C.sub.4 alkyl group;
R.sub.5 denotes a hydrogen atom, a C.sub.1 -C.sub.12 alkyl radical,
a C.sub.3 -C.sub.12 alkenyl radical, a C.sub.3 -C.sub.8 cycloalkyl
radical, an aryl radical, an arylalkyl radical or a hydroxyalkyl
or aminoalkyl radical in which the alkyl radical has 1 to 6 carbon
atoms;
X denotes a hydrogen atom, a halogen atom, a C.sub.1 -C.sub.6 alkyl
radical, a nitro group, a benzoyloxy group or a group --NHR.sub.6
in which R.sub.6 denotes a hydrogen atom, an acyl radical or a C.sub.1
-C.sub.6 alkyl radical;
Z denotes sulfur or oxygen; with the proviso that Z denotes sulfur
when X denotes hydrogen or when R.sub.5 denotes an aryl radical;
Y denotes oxygen or OSO.sub.3 ;
and the addition salts with cosmetically and pharmaceutically acceptable
acids; with the exception of the compounds 2,4-diamino-6-hydroxy-5-bromopyrimidine
3-oxide and 2,4-diamino-6-thiophenylpyrimidine 3-oxide and their
addition salts with acids.
Hair loss description
The present invention relates to new compositions for slowing down
hair loss and for inducing and stimulating its growth, based on
2,4-diaminopyrimidine 3-oxide derivatives, as well as to the new
compounds used in these compositions.
2,4-Diamino-6-piperidinopyrimidine 3-oxide or minoxidil is already
known in the state of the art for its antihypertensive qualities
but also for its use in the treatment of hair loss, of pelade, of
desquamative dermatitis and of alopecia.
The Applicant has discovered new compositions for the treatment
and prevention of hair loss, used particularly in topical application,
containing a particular family of 6-alkoxy- or 6-thioalkyl-2,4-diaminopyrimidine
3-oxide compounds which can be substituted at position 5.
The compounds retained by the Applicant are, surprisingly, very
effective for hair regrowth and particularly for inducing and stimulating
its growth. Additionally, they have a remarkable solubility in the
media normally used in cosmetics or pharmaceuticals.
The subject of the invention is thus new compositions intended
for the treatment and prevention of hair loss which contain particular
6-alkoxy- or 6-thioalkyl-2,4-diaminopyrimidine 3-oxide compounds,
optionally substituted at position 5.
Another subject of the invention is new compounds used in these
compositions.
Another subject of the invention is the use of these particular
compounds for the preparation of a medicament intended for the therapeutic
treatment of hair loss.
Other subjects will become apparent in the course of the description
and examples which follow.
The compositions in accordance with the invention essentially comprise,
in a physiologically acceptable medium, at least one compound corresponding
to the formula (I): ##STR2## in which: R.sub.1 and R.sub.3 denote
a hydrogen atom;
R.sub.2 and R.sub.4, which are identical or different, represent
a hydrogen atom or a C.sub.1 -C.sub.4 alkyl group;
R.sub.5 denotes a hydrogen atom, a C.sub.1 -C.sub.12 alkyl radical,
a C.sub.3 -C.sub.12 alkenyl radical, a C.sub.3 -C.sub.8 cycloalkyl
radical, an aryl radical, an arylalkyl radical or a hydroxyalkyl
or aminoalkyl radical in which the alkyl radical has 1 to 6 carbon
atoms;
X denotes a hydrogen atom, a halogen atom, a C.sub.1 -C.sub.6 alkyl
radical, a nitro group, a benzoyloxy group or a group --NHR.sub.6
in which R.sub.6 denotes a hydrogen atom, an acyl radical or a C.sub.1
-C.sub.6 alkyl radical;
Z denotes sulfur or oxygen, with the proviso that Z denotes sulfur
when X denotes hydrogen or when R.sub.5 denotes an aryl radical;
Y denotes oxygen or OSO.sub.3 ;
as well as its addition salts with physiologically acceptable acids.
The halogen atoms in the structure of formula (I) are preferably
chlorine, bromine, fluorine or iodine.
The C.sub.1 -C.sub.6 alkyl radicals are preferably chosen from
methyl, ethyl, propyl, n-butyl, n-pentyl and n-hexyl.
The C.sub.1 -C.sub.12 alkyl radicals are preferably chosen from
methyl, ethyl, propyl, 2-ethylhexyl, decyl, octyl and dodecyl.
The C.sub.3 -C.sub.12 alkenyl groups are preferably chosen from
allyl, n-butenyl, hexenyl and dodecenyl.
The aryl or aralkyl radicals are preferably chosen from phenyl,
benzyl and tolyl.
The compounds of formula (I) according to the invention can be
converted into their addition salts with pharmaceutically or cosmetically
acceptable acids such as the salts of sulfuric, hydrochloric, hydrobromic,
phosphoric, acetic, benzoic, salicylic, glycolic, succinic, tartaric,
nicotinic, maleic, pamoic, methanesulfonic, picric and lactic acids,
etc.
The compounds of general formula (I) are novel with the exception
of the compound 2,4-diamino-6-hydroxy-5-bromopyrimidine 3-oxide
described in the document W. L. F. Armarego and P. Waring, Aust.
J. Chem., 1981, 34 (9), 1921-33 and the compound 2,4-diamino-6-thiophenylpyrimidine
3-oxide described in the document W. B. Cowden and N. W. Jacobsen,
Aust. J. Chem., 1979, 32 (9), 2049-57.
The compounds in accordance with the present invention can be obtained
from compounds derived from 2,4-diaminopyrimidine 3-oxide, of formula:
##STR3## in which: R.sub.1 and R.sub.3 denote a hydrogen and R.sub.2
and R.sub.4 denote a hydrogen or a C.sub.1 -C.sub.4 alkyl radical
and X' denotes a hydrogen or a C.sub.1 -C.sub.6 alkyl radical or
a group --NHR.sub.6 where R.sub.6 denotes an alkyl radical or a
C.sub.1 -C.sub.6 acyl radical.
The particular starting compounds of the following formula (IIA):
##STR4## are obtained by cyclization of guanidine (1) with an alkyl
cyanoacetate of the formula (2), followed by a halogenation at position
6 of the 2,4-diaminopyrimidine derivative of formula (3) obtained.
An oxidation at position 3 of the pyrimidine ring is then carried
out, preferably in a polar protic solvent in the presence of a percarboxylic
acid R'CO.sub.3 H where R' denotes an alkyl or aryl radical. This
process can be represented by the following scheme: ##STR5##
The particular starting compounds of the following formula (IIB
): ##STR6## with R.sub.3 =H and different from R.sub.4, can be obtained
in a first step by cyclization of guanidine with diethyl malonate,
optionally monosubstituted at the alpha-position, followed by a
chlorination reaction of the pyrimidine derivative thus obtained.
The amine NHR.sub.3 R.sub.4 is then introduced by nucleophilic aromatic
substitution on the pyrimidine ring of the product obtained and
then an oxidation at position 3 is carried out, according to the
principle described previously. This process can be represented
by the following scheme: ##STR7##
The particular starting compounds of formula (IIC): ##STR8## in
which R.sub.1 denotes hydrogen and R.sub.2 denotes alkyl, are obtained
by oxidation, by means of a peracid, of the pyrimidine derivative
of formula: ##STR9## where R" denotes an aryl or an alkyl radical,
followed by a nucleophilic aromatic substitution, of the group --SO.sub.2
R" obtained, by the amine NHR.sub.1 R.sub.2 on the pyrimidine
range. An oxidation at position 3 of the pyrimidine range is then
carried out under the same conditions as previously.
The particular starting compounds of the following formula: ##STR10##
in which R.sub.1 and R.sub.3 denote hydrogen and R.sub.2 and R.sub.4
denote alkyl, can be obtained according to the following reaction
scheme: ##STR11##
Starting from the compound of formula (8), two equivalents of the
amine NHR.sub.3 R.sub.4 are introduced into the pyrimidine ring
and then, after separating on silica gel the products (9) and (9')
formed, the second amine NHR.sub.1 R.sub.2 is introduced.
An oxidation at position 3 of the pyrimidine ring is then carried
out as previously.
The particular compounds of the present invention of the following
formula: ##STR12## where R.sub.1, R.sub.2, R.sub.3, R.sub.4, Z and
R.sub.5 have the same meanings indicated above in the general formula
(I), and X denotes hydrogen, a C.sub.1 -C.sub.6 alkyl radical or
a group --NHR.sub.6 where R.sub.6 denotes a C.sub.1 -C.sub.6 alkyl
radical or an acyl radical, can be obtained by reacting the compounds
of formula (II), either with an alkoxide W.sup.+ OR.sub.5.sup.-
in the corresponding alcohol R.sub.5 OH, where W denotes an alkali
metal such as sodium, potassium or lithium, or with a thiolate W.sup.+
SR.sub.5.sup.- in the presence of a solvent such as dimethylformamide.
This process can be represented by the following reaction scheme:
##STR13##
The particular compounds of the invention of the following formula:
##STR14## where R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5 and
Z have the same meanings indicated above and X denotes a halogen
atom, can be obtained by reacting a compound of formula (II) in
which X' denotes hydrogen with a halogenating agent. In the case
where X denotes chlorine, iodine or bromine, an N-halosuccinimide
of formula (III): ##STR15## for example, is used in the presence
of an alcohol such as methanol.
The chlorine atom at position 6 of the pyrimidine ring is then
substituted by the group --ZR.sub.5 according to the process described
above in Scheme A.
The process can be represented by the following scheme: ##STR16##
The particular compounds of the invention of the following formula
##STR17## can be obtained from the compounds of formula (IA) where
X denotes hydrogen. An electrophilic aromatic substitution reaction
is carried out using a nitrating agent, such as nitric acid, in
the presence of concentrated sulfuric acid.
This process can be represented by the following reaction scheme:
##STR18##
The particular compounds of the invention of the following formula:
##STR19## can be obtained from the compounds of formula (IC) by
catalytic reduction. Palladium on charcoal under a hydrogen atmosphere
is used in particular.
This process can be represented by the following scheme: ##STR20##
The particular compounds of the invention of the following formula:
##STR21## can be obtained by the action of dibenzoyl peroxide in
acetic acid medium on a compound of formula (IA), in which X' denotes
hydrogen, according to the following reaction scheme: ##STR22##
The particular compounds of the invention of general formula (I)
in which Y denotes an oxygen atom can be converted into their O-sulfate
homologs of formula (IF) defined below by chemical sulfating according
to the conventional methods described in the literature (J. Med.
Chem., 1983, 26, pages 1791-1793).
The sulfur trioxide-pyridine, sulfur trioxidetriethylamine or sulfur
trioxide-ethyldiisopropylamine complexes are used as sulfating reagent.
The solvents used are preferably dimethylformamide, chloroform
or acetonitrile or their binary mixtures.
The temperature is of the order of 0.degree. to 25.degree. C. and
the reaction time varies from 1 to 24 hours. ##STR23##
Among the compounds of the invention of general formula (I) in
which Z denotes oxygen, the particularly preferred compounds are
those for which R.sub.1, R.sub.2, R.sub.3 and R.sub.4 denote hydrogen,
X denotes chlorine or the nitro group and R.sub.5 denotes n-butyl.
Among the compounds of the invention of formula (I) in which Z
denotes sulfur, the particularly preferred compounds are those for
which X denotes chlorine or the nitro group, R.sub.1, R.sub.2, R.sub.3
and R.sub.4 denote a hydrogen atom and R.sub.5 denotes methyl, ethyl,
n-butyl, 2-hydroxyethyl, 2-aminoethyl or phenyl.
The compositions in accordance with the present invention, which
contain, in a physiologically acceptable medium, at least one compound
corresponding to the formula (I) or one of its addition salts with
physiologically acceptable acids, can be applied in the cosmetics
or pharmaceutical field, particularly in topical application. They
are intended for the treatment and the prevention of hair loss,
and particularly of pelade and alopecia as well as of desquamative
dermatitis, and the stimulation of hair regrowth.
These compositions can contain, as physiologically acceptable medium,
any medium suitable for topical application, either in cosmetics
or in pharmaceuticals, and which is compatible with the active substance.
The compounds in accordance with the invention can be found in
this medium contained either in the dissolved state or in the dispersed
state, in particular in the micronized form.
The compositions intended to be used as pharmaceuticals are present
in the form of an ointment, tincture, cream, pomade, powder, patch,
impregnated pad, solution, emulsion or vesicular dispersion, lotion,
gel, spray or suspension. They can be either anhydrous or aqueous
according to the clinical indication.
The compounds according to the invention are present in these pharmaceutical
compositions at concentrations of between 0.1 and 10% by weight,
and in particular of between 0.2 and 5% by weight.
The cosmetic compositions are particularly intended to be used
in the form of a lotion, gel, soap, shampoo, aerosol or foam and
contain, in a cosmetically acceptable carrier, at least one compound
of formula (I) or one of its addition salts with acids.
The concentration of these compounds of formula (I) in these compositions
is, preferably, of between 0.01 and 5% by weight and in particular
between 0.05 and 3% by weight.
The compositions in accordance with the invention can contain various
additives normally used in cosmetics or in pharmaceuticals and,
in particular, active substances, for example hydrating agents,
such as thiamorpholine and its derivatives or urea; antiseborrheic
agents such as S-carboxymethylcysteine, S-benzylcysteamine and their
derivatives; and thioxolone.
The compounds in accordance with the invention can be combined
with compounds which further improve their activity towards the
regrowth and/or slowing down of hair loss, such as the following
compounds:
nicotinic acid esters, more particularly C.sub.1 -C.sub.6 alkyl
nicotinates and particularly methyl nicotinate or benzyl nicotinate;
steroidal and nonsteroidal anti-inflammatory agents well known
in the state of the art and in particular hydrocortisone, its salts
and its derivatives, and niflumic acid;
retinoids and more particularly all-trans-retinoic acid, also called
tretinoin, isotretinoin, retinol or vitamin A and its derivatives,
such as the acetate, the palmitate or the propionate, motretinide,
etretinate or zinc all-trans-retinoate;
antibacterial agents chosen more particularly from the macrolides,
the pyranosides and the tetracyclines and particularly erythromycin;
calcium antagonist agents, such as, more particularly, cinnarizine
and diltiazem;
hormones, such as estriol or analogs or thyroxine and its salts;
antiandrogenic agents, such as oxendolone, spironolactone or diethylstilbestrol;
OH radical scavengers, such as dimethyl sulfoxide.
It is also possible to combine with the compounds of the invention,
optionally mixed with others, compounds such as diazoxide, corresponding
to 3-methyl-7-chloro-[2H]-1,2,4-benzothiadiazine 1,1-dioxide; spiroxasone
or 7-(acetylthio)-4',5'-dihydrospiro[androst-4-ene-17,2'-(3'H)furan]-3-one;
p hospholipids, such as lecithin; linoleic and linolenic acids;
salicylic acid and its derivatives described in French Patent 2,581,542,
and more particularly the salicylic acid derivatives which carry
an alkanoyl group having 2 to 12 carbon atoms at position 5 of the
benzene ring; hydroxycarboxylic or ketocarboxylic acids and their
esters, lactones and their corresponding salts; anthralin or 1,8,9-trihydroxyanthracene,
the carotenoids, 5,8,11,14-eicosatetraynoic or 5,8,11-eicosatriynoic
acid, their esters and amides.
The compounds in accordance with the invention can also be combined
with surface-active agents, particularly those chosen from the nonionic
and amphoteric surface-active agents.
Among the nonionic surfactants, there are to be mentioned the polyhydroxypropyl
ethers described particularly in the French Patents Nos. 1,477,048;
2,091,516; 2,169,787; 2,328,763; 2,574,786; the oxyethylenated (C.sub.8
-C.sub.9)-alkylphenols containing 1 to 100 mol of ethylene oxide
and preferably 5 to 35 mol of ethylene oxide; the alkylpolyglycosides
of formula:
in which n varies from 8 to 15 inclusive and x from 1 to 10 inclusive.
Among the amphoteric surface-active agents, there are to be mentioned
more particularly the amphocarboxyglycinates and the amphocarboxypropionates
defined in the CTFA dictionary, 3rd edition, 1982, and sold, particularly,
under the name Miranol.RTM. by the Miranol Company.
The compounds according to the invention can be introduced into
carriers which further improve the activity as regards regrowth
while, at the same time, having advantageous properties at the cosmetic
level, such as volatile ternary mixtures of alkyl ethers of alkylene
glycols, in particular C.sub.1 -C.sub.4 alkyl ethers of C.sub.1
-C.sub.4 alkylene glycols or dialkylene glycols, preferably C.sub.1
-C.sub.4 dialkylene glycols, ethyl alcohol and water, the glycol
solvent more particularly denoting ethylene glycol monoethyl ether,
propylene glycol monomethyl ether or diethylene glycol monomethyl
ether.
The compounds in accordance with the invention can also be introduced
into gelled or thickened carriers, such as essentially aqueous carriers
gelled with heterobiopolysaccharides, such as xanthan gum, scleroglucans
or cellulose derivatives, aqueous-alcoholic carriers gelled with
polyhydroxyethyl acrylates or methacrylates, or essentially aqueous
carriers thickened in particular with polyacrylic acids crosslinked
by a polyfunctional agent, such as the Carbopol products sold by
the Goodrich Company.
These compositions can also contain preserving agents, stabilizing
agents, pH regulating agents, agents for modifying osmetic pressure,
emulsifying agents, UVA and UVB filters and antioxidant agents,
such as .alpha.-tocopherol, butylhydroxyanisole or butylhydroxytoluene.
The physiologically acceptable medium can consist of water or a
mixture of water and a solvent or a mixture of solvents, the solvents
being chosen from the organic solvents acceptable at the cosmetic
or pharmaceutical level and chosen more particularly from the lower,
C.sub.1 -C.sub.4 alcohols, such as ethyl alcohol, isopropyl alcohol
or tert-butyl alcohol, the alkylene glycols or the alkyl ethers
of alkylene glycol and of dialkylene glycol, such as ethylene glycol
monoethyl ether, propylene glycol monomethyl ether or diethylene
glycol monomethyl ether. The solvents, when they are present, are
present in proportions of between 1 and 80% by weight in relation
to the total weight of the composition.
The thickening agents are preferably present in proportions of
between 0.1 and 5% by weight and in particular between 0.4 and 3%
by weight in relation to the total weight of the composition.
Another subject of the invention is a process for cosmetic treatment
of hair or of the scalp, consisting in applying to them at least
one composition such as is defined above, with the aim of improving
the attractiveness of the hair.
Another subject of the invention consists in the use of the composition
containing the compounds of formula (I) defined above for the preparation
of a medicament which has the effect of inducing or stimulating
hair growth and of slowing down its loss.
The treatment principally consists in applying the composition
such as is defined above to the alopecic areas of the scalp of an
individual.
The preferred method of application consists in applying 1 to 2
g of the composition to the alopecic area, at a frequency of one
to two applications per day, for 1 to 7 days per week for a period
of 1 to 6 months.
The compositions can particularly be used in the treatment of pelade,
hair loss and desquamative dermatitis.
The following examples are intended to illustrate the invention
without having any limiting character.
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