Hair loss abstract
Methods and compositions for induction or stimulation of hair growth
and retardation of hair loss are provided. Preferably, these compounds
will include a perhalogenated alkyl radical having 1 to 4 carbon
atoms.
Hair loss claims
What is claimed is:
1. A method for inducing and/or stimulating hair growth and/or
slowing down hair loss in a human or animal in need of same, said
method comprising applying to the hair and/or scalp of said human
or animal, in an amount effective to induce and/or stimulate hair
growth and/or to slow down hair loss, at least one compound having
the formula (I): ##STR2##
in which
R.sub.1 is a cyano group, a halogen atom or an alkyl group having
from 1 to 4 carbon atoms, substituted by at least one halogen atom;
R.sub.2 is a cyano group;
R.sub.3 is an alkyl group having 1 or 2 carbon atoms, optionally
substituted by at least one halogen atom;
R.sub.4 is a hydrogen atom or an alkyl group having from 1 to 4
carbon atoms, substituted by at least one halogen atom, or an aryl
group, optionally substituted by one or more halogen atoms or by
one or more hydroxyl, carboxyl, nitro, cyano, linear or branched
alkyl having 1 to 4 carbon atoms, linear or branched alkoxy having
1 to 4 carbon atoms, linear or branched alkanoyl having 1 to 4 carbon
atoms, or perfluoroalkyl groups; or at least one of its isomers,
at least one of its acylated forms or at least one of its salts;
and optionally rinsing said compound from the hair and/or scalp.
2. The method according to claim 1, wherein R.sub.1 is a chlorine,
bromine or fluorine atom.
3. The method according to claim 2, wherein R.sub.1 is a chlorine
atom.
4. The method according to claim 1, wherein R.sub.1 is an alkyl
group having from 1 to 4 carbon atoms, substituted by at least one
chlorine, bromine or fluorine atom.
5. The method according to claim 4, wherein R.sub.1 is an alkyl
group having from 1 to 4 carbon atoms, substituted by at least one
fluorine atom.
6. The method according to claim 5, wherein R.sub.1 is a perhalogenated
alkyl radical having from 1 to 4 carbon atoms.
7. The method according to claim 6, wherein R.sub.1 is a perhalogenated
methyl radical.
8. The method according to claim 7, wherein R.sub.1 is a perfluorinated
methyl radical.
9. The method according to claim 1, wherein R.sub.3 is a methyl
radical or a perfluorinated methyl radical.
10. The method according to claim 1, wherein R.sub.4 is an alkyl
group having from 1 to 4 carbon atoms, substituted by at least one
chlorine, bromine or fluorine atom.
11. The method according to claim 10, wherein R.sub.4 is an alkyl
group having from 1 to 4 carbon atoms, substituted by at least one
fluorine atom.
12. The method according to claim 10, wherein the substituted alkyl
group is a perhalogenated alkyl group.
13. The method according to claim 12, wherein the perhalogenated
alkyl group is a perhalogenated methyl radical.
14. The method according to claim 1, wherein R.sub.4 is a phenyl
radical.
15. The method according to claim 1, wherein the compound of formula
(I) is
N-(4-cyano-3-(trifluoromethyl)phenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpro
pionamide,
N-(3-chloro 4-cyanophenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpropionamide,
N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-2-phenylpropionamide,
or
N-(3,4-dicyanophenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpropionamide.
16. The method according to claim 1, wherein the compound of formula
(I) is applied in the form of a cosmetic composition comprising
said compound and a cosmetically acceptable carrier, said compound
being present at a concentration of between 10.sup.-6 % and 5%,
by weight, with respect to the total weight of the composition.
17. The method according to claim 16, wherein said compound is
present at a concentration of between 10.sup.-3 % and 1%, by weight,
with respect to the total weight of the composition.
18. The method according to claim 1, wherein the compound of formula
(I) is applied in the form of a pharmaceutical composition comprising
said compound and a pharmaceutically acceptable carrier, said compound
being present at a concentration of between 10.sup.-5 % and 10%,
by weight, with respect to the total weight of the composition.
19. The method according to claim 18, wherein said compound is
present at a concentration of between 10.sup.-2 % and 2%, by weight,
with respect to the total weight of the composition.
20. A topical cosmetic or pharmaceutical composition comprising,
in an amount effective to induce and/or stimulate hair growth and/or
to slow hair loss upon topical application to the scalp or hair,
at least one compound having the formula (I): ##STR3##
in which
R.sub.1 is a cyano group, a halogen atom or an alkyl group having
from 1 to 4 carbon atoms, substituted by at least one halogen atom;
R.sub.2 is a cyano group;
R.sub.3 is an alkyl group having 1 or 2 carbon atoms, optionally
substituted by at least one halogen atom;
R.sub.4 is a hydrogen atom or an alkyl group having from 1 to 4
carbon atoms, substituted by at least one fluorine atom, or an aryl
group, optionally substituted by one or more halogen atoms or by
one or more hydroxyl, carboxyl, nitro, cyano, linear or branched
alkyl having 1 to 4 carbon atoms, linear or branched alkoxy having
1 to 4 carbon atoms, linear or branched alkanoyl having 1 to 4 carbon
atoms, or perfluoroalkyl groups; or at least one of its isomers,
at least one of its acylated forms or at least one of its salts;
and a cosmetically or pharmaceutically acceptable topical carrier
therefor; said composition being in the form of a topical lotion,
gel, emulsion, cream or aerosol or pump-action spray.
21. The composition according to claim 20, wherein the compound
of formula (I) is
N-(4-cyano-3-(trifluoromethyl)phenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpro
pionamide,
N-(3-chloro-4-cyanophenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpropionamide,
N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-2-phenylpropionamide,
or
N-(3,4-dicyanophenyl)-3,3,3-trifluoro2-hydroxy-2-methylpropionamide.
22. A method for inducing and/or stimulating hair growth and/or
slowing down hair loss in a human or animal in need of same, said
method comprising applying to the hair and/or scalp of said human
or animal, in an amount effective to induce and/or stimulate hair
growth and/or to slow down hair loss, at least one compound having
the formula (I): ##STR4##
in which
R.sub.1 is a cyano group, a halogen atom or an alkyl group having
from 1 to 4 carbon atoms, substituted by at least one halogen atom;
R.sub.2 is a cyano group or a halogen atom;
R.sub.3 is an alkyl group, having 1 or 2 carbon atoms, optionally
substituted by at least one halogen atom;
R.sub.4 is a perfluorinated methyl radical; or R.sub.4 is an aryl
group optionally substituted by one or more halogen atoms or by
one or more hydroxyl, carboxyl, nitro, cyano, linear or branched
alkyl having 1 to 4 carbon atoms, linear or branched alkoxy having
1 to 4 carbon atoms, linear or branched alkanoyl having 1 to 4 carbon
atoms, or perfluoroalkyl groups; or at least one of its isomers,
at least one of its acylated forms or at least one of its salts;
and optionally rinsing said compound from the hair and/or scalp.
23. The method according to claim 22, wherein R.sub.1 is a chlorine,
bromine or fluorine atom.
24. The method according to claim 23, wherein R.sub.1 is a chlorine
atom.
25. The method according to claim 22, wherein R.sub.1 is an alkyl
group having from 1 to 4 carbon atoms, substituted by at least one
chlorine, bromine or fluorine atom.
26. The method according to claim 25, wherein R.sub.1 is an alkyl
group having from 1 to 4 carbon atoms, substituted by at least one
fluorine atom.
27. The method according to claim 26, wherein R.sub.1 is a perhalogenated
alkyl radical having from 1 to 4 carbon atoms.
28. The method according to claim 27, wherein R.sub.1 is a perhalogenated
methyl radical.
29. The method according to claim 28, wherein R.sub.1 is a perfluorinated
methyl radical.
30. The method according to claim 22, wherein R.sub.2 is a chlorine,
bromine or fluorine atom.
31. The method according to claim 30, wherein R.sub.2 is a chlorine
atom.
32. The method according to claim 22, wherein R.sub.3 is a methyl
radical or a perfluorinated methyl radical.
33. The method according to claim 22, wherein R.sub.4 is a perfluorinated
methyl radical.
34. The method according to claim 22, wherein R.sub.4 is a phenyl
radical.
35. The method according to claim 22, wherein the compound of formula
(I) is
N-(4-cyano-3-(trifluoromethyl)phenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpro
pionamide,
N-(3-chloro-4-cyanophenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpropionamide,
N-(3,4-dichlorophenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpropionamide,
N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-2-phenylpropionamide,
or
N-(3,4-dicyanophenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpropionamide.
36. The method according to claim 22, wherein the compound of formula
(I) is applied in the form of a cosmetic composition comprising
said compound and a cosmetically acceptable carrier, said compound
being present at a concentration of between 10.sup.-6 % and 5%,
by weight, with respect to the total weight of the composition.
37. The method according to claim 36, wherein said compound is
present at a concentration of between 10.sup.-3 % and 1%, by weight,
with respect to the total weight of the composition.
38. The method according to claim 22, wherein the compound of formula
(I) is applied in the form of a pharmaceutical composition comprising
said compound and a pharmaceutically acceptable carrier, said compound
being present at a concentration of between 10.sup.-5 % and 10%,
by weight, with respect to the total weight of the composition.
39. The method according to claim 38, wherein said compound is
present at a concentration of between 10.sup.-2 % and 2%, by weight,
with respect to the total weight of the composition.
40. A topical cosmetic or pharmaceutical composition comprising,
in an amount effective to induce and/or stimulate hair growth and/or
to slow hair loss upon topical application to the scalp or hair,
at least one compound having the formula (I): ##STR5##
in which
R.sub.1 is a cyano group, a halogen atom or an alkyl group having
from 1 to 4 carbon atoms, substituted by at least one halogen atom;
R.sub.2 is a cyano group or a halogen atom;
R.sub.3 is an alkyl group having 1 or 2 carbon atoms, optionally
substituted by at least one halogen atom;
R.sub.4 is a perfluorinated methyl radical; or R.sub.4 is an aryl
group optionally substituted by one or more halogen atoms or by
one or more hydroxyl, carboxyl, nitro, cyano, linear or branched
alkyl having 1 to 4 carbon atoms, linear or branched alkoxy having
1 to 4 carbon atoms, linear or branched alkanoyl having 1 to 4 carbon
atoms, or perfluoroalkyl groups; or at least one of its isomers,
at least one of its acylated forms or at least one of its salts;
and a cosmetically or pharmaceutically acceptable topical carrier
therefor; said composition being in the form of a topical lotion,
gel, emulsion, cream or aerosol or pump-action spray.
41. The composition according to claim 40, wherein R.sub.4 is a
perfluorinated methyl radical.
42. The composition according to claim 41, wherein R.sub.4 is a
phenyl radical.
43. The composition according to claim 40, wherein the compound
of formula (I) is
N-(4-cyano-3-(trifluoromethyl)phenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpro
pionamide,
N-(3-chloro-4-cyanophenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpropionamide,
N-(3,4-dichlorophenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpropionamide,
N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-2-phenylpropionamide,
or
N-(3,4-dicyanophenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpropionamide.
Hair loss description
The present invention relates to the use as active principle, in
a physiologically acceptable medium, in a cosmetic composition or
for the preparation of a pharmaceutical composition, of an effective
amount of at least one specific compound from the family of the
N-aryl-2-hydroxyalkylamides, intended to induce and/or stimulate
hair growth and/or to slow down hair loss.
In man, hair growth and its renewal are mainly determined by the
activity of the hair follicles. Their activity is cyclical and essentially
comprises three phases, namely the anagen phase, the catagen phase
and the telogen phase.
The active anagen phase or growth phase, which lasts several years
and during which the hair lengthens, is succeeded by a very short
and transitory catagen phase, which lasts a few weeks, and then
by a resting phase, also known as the telogen phase, which lasts
a few months.
At the end of the period of rest, the hairs fall out and another
cycle commences. The head of hair is thus constantly renewed and
at any moment, out of the approximately 150,000 hairs which a head
of hair comprises, approximately 10% of them are at rest and will
thus be replaced in a few months.
However, various causes can result in a significant, temporary
or permanent, hair loss. Alopecia is essentially due to a disturbance
of hair renewal which results, firstly, in an acceleration in the
frequency of the cycles at the expense of the quality of the hair
and then of its amount. A gradual thinning of the head of hair takes
place by regression of the so-called "terminal" hairs
at the downy stage. Areas are preferentially affected, in particular
the temples or the front of the head in men, and, in women, a diffuse
alopecia of the vertex is observed.
The term alopecia covers a whole family of conditions of the hair
follicle having, as final consequence, partial or general permanent
hair loss. In a significant number of cases, early hair loss takes
place in genetically predisposed subjects and it effects men in
particular. It relates more particularly to androgenetic or androgenic
or even androgeno-genetic alopecia.
There has been a search for many years, in the cosmetic or pharmaceutical
industry, for substances which make it possible to eliminate or
reduce alopecia and in particular to induce or stimulate hair growth
or to decrease hair loss.
From this viewpoint, a large number of very diverse active compounds
have certainly already been provided, such as, for example, 2,4-diamino-6-piperidinopyrimidine
3-oxide or "Minoxidil", disclosed in Patents U.S. Pat.
No. 4,139,619 and U.S. Pat. No. 4,596,812, or its numerous derivatives,
such as those disclosed, for example, in Patent Applications EP
0,353,123, EP 0,356,271, EP 0,408,442, EP 0,522,964, EP 0,420,707,
EP 0,459,890 and EP 0,519,819.
It remains generally the case that it would be advantageous and
useful to be able to have available active compounds other than
those already known which are potentially more active and/or less
toxic.
This aim and others are achieved by the present invention which
relates to the use as active principle, in a physiologically acceptable
medium, in a cosmetic composition or for the preparation of a pharmaceutical
composition, of an effective amount of at least one compound corresponding
to the general formula (I): ##STR1##
in which
R.sub.1 is a cyano group, a halogen atom or an alkyl group, having
from 1 to 4 carbon atoms, substituted by at least one halogen atom;
R.sub.2 is a cyano group or a halogen atom;
R.sub.3 is an alkyl group, having 1 or 2 carbon atoms, optionally
substituted by at least one halogen atom;
R.sub.4 is a hydrogen atom or an alkyl group, having from 1 to
4 carbon atoms, substituted by at least one halogen atom, or an
aryl group, optionally substituted by one or more halogen atoms
or by one or more hydroxyl, carboxyl, nitro, cyano, linear or branched
alkyl, having 1 to 4 carbon atoms, linear or branched alkoxy, having
1 to 4 carbon atoms, linear or branched alkanoyl, having 1 to 4
carbon atoms, or perfluoroalkyl groups;
or of at least one of its isomers, of at least one of its acylated
forms or alternatively of at least one of its salts;
this compound or the pharmaceutical composition being intended
to induce and/or stimulate hair growth and/or to slow down hair
loss.
These compounds exhibit notable activities which justify their
use as active principle for inducing and/or stimulating hair growth
and/or slowing down hair loss.
This is because they are excellent openers of potassium channels,
the main property of Minoxidil, the only compound recognized to
date as effective in the treatment of hair loss
They are also excellent receptorial antagonists of androgens, androgens
being responsible for a particularly widespread form of alopecia,
androgen-dependent alopecia.
To the knowledge of the Applicant Company, provision has never
been made in the prior art for the use of such compounds possessing
mixed activity, openers of potassium channels/antiandrogens, for
controlling hair loss.
According to a specific embodiment of the invention, R.sub.1. can
be a chlorine, bromine or fluorine atom, preferably a chlorine atom.
According to another embodiment of the invention, R.sub.1, can
be an alkyl group, having from 1 to 4 carbon atoms, substituted
by at least one chlorine, bromine or fluorine atom. R.sub.1, is
preferably an alkyl group, having from 1 to 4 carbon atoms, substituted
by at least one fluorine atom, more preferably R.sub.1, is a perhalogenated
alkyl radical, having from 1 to 4 carbon atoms, more preferably
still R.sub.1, is a perhalogenated methyl radical and more preferably
still R.sub.1, is a perfluorinated methyl radical.
When R.sub.2 is a halogen atom, R.sub.2 can be a chlorine, bromine
or fluorine atom; R.sub.2 is preferably a chlorine atom.
R.sub.3 is preferably a methyl radical or a perfluorinated methyl
radical.
When R.sub.4 is an alkyl group, having from 1 to 4 carbon atoms,
substituted by at least one halogen atom, such as chlorine, bromine
or fluorine, the halogen atom is preferably a fluorine atom.
R.sub.4 is preferably a perhalogenated alkyl radical having from
1 to 4 carbon atoms and, more preferably still, R.sub.4 is a perhalogenated
methyl radical, preferably a perfluorinated methyl radical.
When R4 is an aryl group, it is preferably a phenyl radical.
R.sub.3 and R.sub.4 preferably have a different meaning.
The compound used according to the invention is preferably chosen
from N-(4-cyano-3-(trifluoromethyl)phenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpr
opionamide, N-(3-chloro-4-cyanophenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpropionamide,
N-(3,4-dichlorophenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpropionamide,
N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-2-phenylpropionamide
and N-(3,4-dicyanophenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpropionamide.
These compounds can be used alone or as a mixture.
The effective amount of compound to be used corresponds, of course,
to the amount necessary in order to obtain the desired result. A
person skilled in the art is thus in a position to evaluate this
effective amount, which depends on the nature of the compound used
and on the person thus treated. To give an order of magnitude, according
to the invention, in a cosmetic composition, the compound can be
present at a concentration of between 10.sup.-6 % and 5%, by weight
with respect to the total weight of the composition, and preferably
of between 10.sup.-3 % and 1%. In the preparation of a pharmaceutical
composition, the compound can be used at a concentration of between
10.sup.-5 % and 10%, by weight with respect to the total weight
of the composition, and preferably of between 10.sup.-2 % and 2%.
The pharmaceutical composition according to the invention can be
administered parenterally, enterally or topically. The pharmaceutical
composition is preferably administered topically
The physiologically acceptable medium in which the active principle
is used according to the invention can be anhydrous or aqueous.
Anhydrous medium is understood to mean a solvent medium containing
less than 1% of water. This medium can be composed of a solvent
or of a mixture of solvents chosen more particularly from C.sub.2
-C.sub.4 lower alcohols, such as ethyl alcohol, alkylene glycols,
such as propylene glycol, and alkylene glycol or dialkylene glycol
alkyl ethers, the alkyl or alkylene radicals of which comprise from
1 to 4 carbon atoms. Aqueous medium is understood to mean a medium
consisting of water or a mixture of water and another physiologically
acceptable solvent chosen in particular from the abovementioned
organic solvents. In the latter case, these other solvents, when
they are present, represent approximately 5 to 95% by weight of
the composition.
It is possible for the physiologically acceptable medium to be
able to comprise other adjuvants commonly used in the cosmetic or
pharmaceutical field, such as surface-active agents, thickening
or gelling agents, cosmetic agents, preservatives, or basifying
or acidifying agents well known in the state of the art, and in
amounts sufficient for the desired presentation form to be obtained,
in particular the more or less thickened lotion form, the gel form,
the emulsion form or the cream form. Use can optionally be made
in a form pressurized in an aerosol or vaporized from a pump-action
spray.
It is also possible to use, in combination with the active principle,
compounds which further improve the activity with respect to hair
regrowth and/or with respect to slowing down hair loss and which
have already been described for this activity.
Mention may more particularly be made, among the latter compounds,
without implied limitation, of:
nicotinic acid esters, including in particular tocopherol nicotinate,
benzyl nicotinate and C.sub.1 -C.sub.6 alkyl nicotinates, such as
methyl or hexyl nicotinates;
pyrimidine derivatives, such as 2,4-diamino-6-piperidinopyrimidine
3-oxide or "Minoxidil" disclosed in Patents U.S. Pat.
No. 4,139,619 and U.S. Pat. No. 4,596,812;
agents which promote hair regrowth, such as those disclosed by
the Applicant Company in the European Patent Application published
under the number 0,648,488;
antibacterial agents, such as macrolides, pyranosides and tetracyclines,
and in particular erythromycin;
calcium antagonists, such as cinnarizine, diltiazem, nimodipine
and nifedipine;
hormones, such as oestriol or analogues, or thyroxine and its salts;
steroidal anti-inflammatory agents, such as corticosteroids (for
example, hydrocortisone);
antiandrogens, such as oxendolone, spironolactone, diethylstilbestrol
and flutamide;
steroidal or non-steroidal 5-.alpha.-reductase inhibitors, such
as finasteride;
potassium agonists, such as cromakalira and nicorandil.
Other compounds can also be added to the above list, namely, for
example, diazoxide, spiroxasone, phospholipids, such as lecithin,
linoleic and linolenic acids, salicylic acid and its derivatives
disclosed in French Patent FR 2,581,542, such as salicylic acid
derivatives carrying an alkanoyl group having from 2 to 12 carbon
atoms at the 5 position of the benzene ring, hydroxycarboxylic or
ketocarboxylic acids and their esters, lactones and their corresponding
salts, anthralin, carotenoids, eicosatetrayenoic and eicosatr yenoic
acids or their esters and amides, vitamin D and its derivatives,
or extracts of plant or bacterial origin.
It is also possible to envisage the composition comprising at least
one compound as defined above being in liposomed form, as disclosed,
in particular, in Patent Application WO 94/22468, filed on Oct.
13, 1994 by the company Anti Cancer Inc. Thus, the compound encapsulated
in the liposomes can be delivered selectively to the hair follicle.
The cosmetic composition according to the invention is to be applied
to the alopecic areas of the scalp and hair of an individual and
is optionally left in contact for several hours and is optionally
to be rinsed out. It is possible, for example, to apply the composition
comprising an effective amount of at least one compound as defined
above in the evening, to keep the composition in contact overnight
and, optionally, to shampoo in the morning. These applications can
be repeated daily for one or more months according to the individual.
Thus, another subject-matter of the present invention is a 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
composition comprising an effective amount of at least one compound
as defined above, in leaving this composition in contact with the
hair and/or the scalp, and optionally in rinsing.
The treatment process exhibits the characteristics of a cosmetic
process insofar as it allows the attractiveness of the hair to be
improved while giving it greater strength and an improved appearance.
Examples will now be given by way of illustration which should
not be understood as limiting in any way the scope of the invention.
Example 1
IC.sub.50 of the Compounds Determined for their Effect on the Potassium
Channels and on the Androgen Receptors
The IC.sub.50 corresponds to the concentration which decreases
by 50% either an induced pharmacological mechanism, such as muscular
contraction, or the attachment of a molecule to its membrane receptor.
In order to determine the IC.sub.50 of the compounds for their
effect on the potassium channels, they were tested according to
the methods of Newgreen et al. (Br. J. Pharmacol., 1990, 100, 605-613),
Bray et al. (Arch. Pharmacol., 1991, 344, 351-359) and wickerden
et al. (Br. J. Pharmacol., 1991, 103, 1148-1152).
In order to determine the IC.sub.50 of the compounds for their
effect on the androgen receptors, they were tested according to
the method of Schilling and Liao ("The Prostate", 1984,
5, 581-588).
The values are given in .mu.M
The following compounds were tested:
A: N-(4-cyano-3-(trifluoromethyl)phenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpr
opionamide,
B: N-(3-chloro-4-cyanophenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpropionamide,
C: N-(3,4-dichlorophenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpropionamide,
D: N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-2-phenylpropionamide,
E: N-(3,4-dicyanophenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpropionamide,
F: N-(4-nitro-3-(trifluoromethyl)phenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpr
opionamide;
G: N-(4-cyanophenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpropionamide.
The compounds F and G, with structures similar to those of the
compounds of the invention but not included within the definition
of the compounds of the invention, were tested as comparatives.
Compound K.sup.+ Channels Androgen receptors A 0.5 1 B 0.1 0.5
C 2 1 D 3 3 E 1 10 F >10 >10 G 10 >10
The molecules A, B, C, D and E exhibit a good affinity for the
androgen receptor and an excellent opening effect for potassium
channels, whereas, in comparison, the molecules F and G, similar
in their structure but not coming within the scope of the invention,
exhibit a poor affinity for the androgen receptor and a poor opening
effect for potassium channels.
EXAMPLE 2
Examples of Compositions Containing an N-aryl-2-hydroxyalkylamide
These compositions are obtained by the usual techniques commonly
used in cosmetics or in pharmaceuticals.
Lotion for Combating Hair Loss:
N-(4-Cyano-3-(trifluoromethyl)phenyl)-3,3,3- 0.1 g trifluoro-2-hydroxy-2-methylpropionamide
Propylene glycol 10.0 g Isopropyl alcohol q.s. for 100.0 g
1 ml of this lotion is applied to the scalp, at the rate of one
to two times daily.
Niosomed Gel:
Chimexane NS .RTM. 1.8 g Monosodium stearoylglutamate 0.2 g N-(4-Cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-
1.0 g 2-phenylpropionamide Carbomer 0.2 g Triethanolamine q.s. pH
= 7 Preservatives q.s. Fragrances q.s. Demineralized water q.s.
for 100.0 g
This gel is applied to the scalp, one to two times daily.
Lotion for Combating Hair Loss:
N-(3-Chloro-4-cyanophenyl)-3,3,3-trifluoro- 0.5 g 2-hydroxy-2-methylpropionamide
Propylene glycol 30.0 g Ethyl alcohol 40.5 g Water q.s. for 100.0
g
This lotion is applied to the scalp, one to two times daily, at
the rate of 1 ml per application.
Thickened Lotion for Combating Hair Loss:
N-(4-Cyano-3-(trifluoromethyl)phenyl)-3,3,3- 0.01 g trifluoro-2-hydroxy-2-methylpropionamide
Kawaine 2.0 g Hydroxypropylcellulose, sold by the company 3.5 g
Hercules under the name Klucel G Ethyl alcohol q.s. for 100.0 g
This thickened lotion is applied to the scalp, one to two times
daily, at the rate of 1 ml per application.
Niosomed Lotion:
Chimexane NL .RTM. 0.475 g Cholesterol 0.475 g Monosodium stearoylglutamate
0.05 g N-(3,4-Dicyanophenyl)-3,3,3-trifluoro-2- 1.0 g hydroxy-2-methylpropionamide
Preservatives q.s. Colorants q.s. Fragrance q.s. Demineralized water
q.s. for 100.0 g
This lotion is applied to the scalp, one to two times daily, at
the rate of 1 ml per application.
Lotion for Combating Hair Loss:
N-(3,4-Dichlorophenyl)-3,3,3-trifluoro- 1.5 g 2-hydroxy-2-methylpropionamide
Propylene glycol monomethyl ether, sold 20.0 g under the name Dowanol
PM by the company Dow Chemical Hydroxypropylcellulose, sold by the
3.0 g company Hercules under the name Klucel G Ethyl alcohol 40.0
g Water q.s. for 100.0 g
This thickened lotion is applied to the scalp, one to two times
daily, at the rate of 1 ml per application.
With each of the compositions described in the above examples,
a slower rate of hair loss and/or a regrowth effect was observed
after several months of treatment and depending on the subjects
treated.
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