Hair loss abstract
A regimen for inducing/stimulating hair growth and/or retarding
hair loss on an individual in need of such treatment, comprising
administering thereto, advantageously topically and for such period
of time as required to elicit the desired effect, an effective amount
of at least one RXR-type retinoid receptor agonist preferably having
the structural formula(I): ##STR1## in which Ar is one of the following
radicals: ##STR2##
Hair loss claims
What is claimed is:
1. A regimen for at least one of inducing or stimulating hair growth
and retarding hair loss on an individual in need of treatment, comprising
administering thereto, for a period of time sufficient to elicit
a desired effect, an effective amount of at least one RXR-type retinoid
receptor agonist.
2. The regimen as defined by claim 1, wherein said at least one
RXR-type retinoid receptor agonist has the following structural
formula (I): ##STR5## in which Ar is selected from the group consisting
of the following substituents: ##STR6## wherein the pentagonal heterocycles
(ii), (iii), (iv), (v) or (vi) are substituted in position 4 or
5; A is --(CH.sub.2).sub.n wherein n ranges from 0 to 5; B is --COOH,
--COOR.sub.7, --CONR.sub.8 R.sub.9, --CH.sub.2 OH, --CH.sub.2 OR.sub.10,
--CH.sub.2 OCOR.sub.10, --CHO, --CH(OR.sub.11).sub.2, --CHOR.sub.12
O, --COR.sub.6, --CR.sub.6 (OR.sub.11).sub.2 or --CR.sub.6 OR.sub.12
O; X is an oxygen atom, --C(R.sub.5).sub.2 or S(O).sub.m wherein
m is 0, 1 or 2; R.sub.1 is a halogen atom or an alkyl substituent
having from 1 to 6 carbon atoms; R.sub.2 is a hydrogen atom, an
alkyl substituent having from 1 to 6 carbon atoms or a halogen atom;
the substituents R.sub.3 are identical or different, and are each
an alkyl substituent having from 1 to 6 carbon atoms, a halogen
atom, --OR.sub.10, --SR.sub.10, --OCOR.sub.10, --SCOR.sub.10, --NH.sub.2,
--NHR.sub.10, --N(R.sub.10).sub.2, --NHCOR.sub.10 or --NR.sub.10
COR.sub.10 ; the substituents R.sub.4 are identical or different,
and are each a hydrogen atom, an alkyl substituent having from 1
to 6 carbon atoms, a halogen atom, an alkoxy substituent having
from 1 to 6 carbon atoms or a thioalkoxy substituent having from
1 to 6 carbon atoms; the substituents R.sub.5 are identical or different,
and are each a hydrogen atom or an alkyl substituent having from
1 to 6 carbon atoms; R.sub.6 is an alkyl substituent having from
1 to 6 carbon atoms, a cycloalkyl substituent having from 3 to 6
carbon atoms or an alkenyl substituent having from 2 to 6 carbon
atoms; R.sub.7 is an alkyl substituent having from 1 to 10 carbon
atoms, a cycloalkyl substituent having from 5 to 10 carbon atoms
or a phenyl or lower alkylphenyl substituent; the substituents R.sub.8
and R.sub.9 are identical or different, and are each a hydrogen
atom, an alkyl substituent having from 1 to 10 carbon atoms, a cycloalkyl
substituent having from 5 to 10 carbon atoms, a phenyl substituent
or a lower alkylphenyl substituent; the substituents R.sub.10 are
identical or different, and are each an alkyl substituent having
from 1 to 10 carbon atoms, a phenyl substituent or a lower alkylphenyl
substituent; R.sub.11 is an alkyl substituent having from 1 to 6
carbon atoms; and R.sub.12 is a divalent alkylene substituent having
from 2 to 5 carbon atoms; or one or more optical or geometrical
isomers or acyl derivatives or pharmaceutically acceptable salts
thereof.
3. The regimen as defined by claim 2, wherein in formula (I), each
halogen atom is a fluorine, chlorine, bromine or iodine atom.
4. The regimen as defined by claim 2, wherein in formula (I), R.sub.1
is an alkyl substituent having from 1 to 6 carbon atoms.
5. The regimen as defined by claim 2, wherein in formula (I), R.sub.2
is a hydrogen atom or an alkyl substituent having from 1 to 6 carbon
atoms.
6. The regimen as defined by claim 2, wherein in formula (I), each
R.sub.3 is an alkyl substituent having from 1 to 6 carbon atoms.
7. The regimen as defined by claim 2, wherein in formula (I), each
R.sub.4 is a hydrogen atom or an alkyl substituent having from 1
to 6 carbon atoms.
8. The regimen as defined by claim 2, wherein in formula (I), each
R.sub.5 is an alkyl substituent having from 1 to 6 carbon atoms.
9. The regimen as defined by claim 2, wherein in formula (I), --A--B--
is the substituent --(CH.sub.2).sub.n --COOR.sub.7, or the substituent
--(CH.sub.2).sub.n --CONR.sub.8 R.sub.9.
10. The regimen as defined by claim 2, wherein said at least one
retinoid receptor agonist is selected from the group consisting
of 2-[(E)-2-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)propen-1-yl]
-4-thiophenecarboxylic acid;
2-[(E)-2-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)propen-1-yl]-
5-thiophenecarboxylic acid;
2-[(E)-2-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethylnaphthalen-2-yl)propen-1-
yl]-4-furancarboxylic acid; 4-[(E)-2-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)propen-1-yl]
benzoicacid; 2-[(E)-2-(4,4,7-trimethyl-6-thiochlomanyl)-propen-1-yl]-4-thiophenecarboxy
lic acid; ethyl 2[(E)-2-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)propen-1-yl]-
4-thiophenecarboxylate; 2-[(E)-2-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)propen-1-yl]
-4-thiazolecarboxylic acid and 2-[(E)-2-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)propen-1-yl]
-5-imidazolecarboxylic acid.
11. The regimen as defined by claim 2, wherein in formula (I),
Ar is the substituent (i).
12. The regimen as defined by claim 2, wherein in formula (I),
Ar is the substituent (ii).
13. The regimen as defined by claim 2, wherein in formula (I),
Ar is the substituent (iii).
14. The regimen as defined by claim 2, wherein in formula (I),
Ar is the substituent (iv).
15. The regimen as defined by claim 2, wherein in formula (I),
Ar is the substituent (v).
16. The regimen as defined by claim 2, wherein in formula (I),
Ar is the substituent (vi).
17. The regimen as defined by claim 2, wherein in formula (I),
X is the substituent --C(R.sub.5).sub.2, Ar is the substituent (iii),
B is --COOH and the R substituents are alkyl or halogen.
18. The regimen as defined by claim 2, wherein said at least one
retinoid receptor agonist is selected from the group consisting
of 2-[(E)-2-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)propen-1-yl]
-4-thiophenecarboxylic acid;
2-[(E)-2-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)propen-1-yl]-
5-thiophenecarboxylic acid, and
ethyl 2[(E)-2-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)propen-1-yl]-
4-thiophenecarboxylate.
19. The regimen as defined by claim 2, wherein said at least one
retinoid receptor agonist is 2-[(E)-2-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethylnaphthalen-2-yl)propen-1
-yl]-4-furancarboxylic acid or 4-[(E)-2-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)propen-1-yl]
benzoic acid.
20. The regimen as defined by claim 2, wherein said at least one
retinoid receptor agonist is 2-[(E)-2-(4,4,7-trimethyl-6-thiochromanyl)propen-1-yl]-4-thiophenecarboxyl
ic acid.
21. The regimen as defined by claim 2, wherein said al least one
retinoid receptor agonist is 2-[(E)-2-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)propen-1-yl]
-4-thiazolecarboxylic acid or 2-[(E)-2-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)propen-1-yl]
-5-imidazolecarboxylic acid.
22. The regimen as defined by claim 1, comprising topically applying
said a least one retinoid receptor agonist to at least one of the
hair and scalp of said individual and then, optionally, rinsing
said at least one retinoid receptor agonist therefrom.
23. A cosmetic or therapeutic composition of matter suited for
at least one of inducing or stimulating hair growth and retarding
hair loss, comprising an effective amount of at least one RXR-type
retinoid receptor agonist, formulated into a cosmetically or therapeutically
acceptable vehicle, diluent or carrier therefor wherein said RXR-type
retinoid receptor agonist has the following structural formula (I):
##STR7## in which Ar is selected from the group consisting of the
following substituents: ##STR8## wherein the pentagonal heterocycles
(ii), (iii), (iv), (v) or (vi) are substituted in position 4 or
5; A is --(CH.sub.2).sub.n wherein n ranges from 0 to 5; B is --COOH,
--COOR.sub.7, --CONR.sub.8 R.sub.9, --CH.sub.2 OH, --CH.sub.2 OR.sub.10,
--CH.sub.2 OCOR.sub.10, --CHO, --CH(OR.sub.11).sub.2, --CHOR.sub.12
O, --COR.sub.6, --CR.sub.6 (OR.sub.11).sub.2 or --CR.sub.6 OR.sub.12
O; X is an oxygen atom --C(R.sub.5).sub.2 or S(O).sub.m wherein
m is 0, 1 or 2; R.sub.1 is a hydrogen atom or an alkyl substituent
having from 1 to 6 carbon atoms; R.sub.2 is a hydrogen atom, an
alkyl substituent having from 1 to 6 carbon atoms or a halogen atom;
the substituents R.sub.3 are identical or different, and are each
an alkyl substituent having from 1 to 6 carbon atoms, a halogen
atom --OR.sub.10, --SR.sub.10, --OCOR.sub.10, --SCOR.sub.10, --NH.sub.2,
--NHR.sub.10, --N(R.sub.10).sub.2, --NHCOR.sub.10 or --NR.sub.10
COR.sub.10 ; the substituents R.sub.4 are identical or different,
and are each a hydrogen atom, an alkyl substituent having from 1
to 6 carbon atoms, a halogen atom, an alkoxy substituent having
from 1 to 6 carbon atoms or a thioalkoxy substituent having from
1 to 6 carbon atoms; the substituents R.sub.5 are identical or different
and are each a hydrogen atom or an alkyl substituent having from
1 to 6 carbon atoms; R.sub.6 is an alkyl substituent having from
1 to 6 carbon atoms, a cycloalkyl substituent having from 3 to 6
carbon atoms or an alkenyl substituent having from 2 to 6 carbon
atoms; R.sub.7 is an alkyl substituent having from 1 to 10 carbon
atoms, a cycloalkyl substituent having from 5 to 10 carbon atoms
or a phenyl or lower alkylphenyl substituent; the substituents R.sub.8
and R.sub.9 are identical or different, and are each a hydrogen
atom, an alkyl substituent having from 1 to 10 carbon atoms, a cycloalkyl
substituent having from 5 to 10 carbon atoms, a phenyl substituent
or a lower alkylphenyl substituent; the substituents R.sub.10 are
identical or different, and are each an alkyl substituent having
from 1 to 10 carbon atoms, a phenyl substituent or a lower alkylphenyl
substituent; R.sub.11 is an alkyl substituent having from 1 to 6
carbon atoms; and R.sub.12 is a divalent alkylene substituent having
from 2 to 5 carbon atoms; or one or more optical or geometrical
isomers or acyl derivatives or pharmaceutically acceptable salts
thereof, and wherein said composition further comprises another
hair growth promoter which is not a RXR-type retinoid receptor agonist.
24. The cosmetic or therapeutic composition as defined by claim
23, comprising from 0.001% to 10% by weight of said at least one
retinoicd receptor agonist.
25. The cosmetic or therapeutic composition as defined by claim
23, comprising from 0.1% to 1% by weight of said at least one retinoid
receptor agonist.
26. The cosmetic or therapeutic composition as defined by claim
24, comprising a lotion, gel, emulsion, cream, aerosol or spray.
Hair loss description
BACKGROUND OF THE INVENTION
1. Technical Field of the Invention
The present invention relates to inducing and/or stimulating hair
growth and/or retarding hair loss by topically/systemically administering
to an individual in need of such treatment an effective amount of
at least one compound which is an agonist with respect to RXR-type
retinoid receptors.
This invention also relates to novel cosmetic/therapeutic compositions
comprising such retinoid receptor agonists for promoting hair growth
and/or retarding hair loss.
2. Description of the Prior Art
In human subjects the growth of the hair and its renewal are principally
determined by the activity of the hair follicles. This activity
is cyclic 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 elongates, is succeeded by a very
short and transitory catagenic phase which lasts for a few weeks,
followed by a rest or quiescent phase, designated the telogenic
phase, which lasts for a few months.
At the end of the rest period, the hair falls out and an new cycle
begins. The head of hair thus undergoes permanent renewal 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 within
a few months.
However, various causes may lead to a considerable temporary or
permanent loss of hair. Alopecia, for example, is essentially due
to a disturbance of hair renewal, which leads, in a first stage,
to acceleration of the frequency of the cycles at the expense of
the hair quality and then at the expense of its quantity. A gradual
thinning of the head of hair occurs, and the so-called "end"
or "terminal" hairs at the down stage recede. Certain
regions are preferentially affected, in particular the temples and
the front of the head in men, and, in women, diffuse alopecia of
the crown is observed.
The term "alopecia" comprehends an entire family of afflictions/conditions
of the hair follicle, the final consequence of which is the permanent
partial or general loss of hair. In a large number of cases, early
hair loss occurs in genetically predisposed individuals and it affects
men in particular. This type of hair loss is more particularly androgenetic
or androgenic or, alternatively, androgeno-genetic alopecia.
Active agents for eliminating or reducing alopecia, and, in particular,
for inducing or stimulating hair growth or for retarding hair loss,
have long been desiderata in the cosmetics and pharmaceutical industries.
From this perspective, a great number of very diverse active compounds
such as, for example, 2,4-diamino-6-piperidinopyrimidine 3-oxide
or "Minoxidil," described in U.S. Pat. Nos. 4,139,619
and 4,596,812, or, alternatively, its many derivatives, such as
those described, for example, in 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, have
to date been proposed.
Need continues to exist in this art, however, for other active
species for modulating hair growth/loss that are more active and/or
less toxic.
SUMMARY OF THE INVENTION
It has now unexpectedly and surprisingly been determined that RXR-type
retinoid receptor agonists are well suited for inducing/stimulating
hair growth and/or retarding hair loss.
DETAILED DESCRIPTION OF BEST MODE AND SPECIFIC/PREFERRED EMBODIMENTS
OF THE INVENTION
More particularly according to the present invention, cosmetic/therapeutic
compositions well suited for promoting hair growth and/or retarding
hair loss are provided by formulating an effective amount of at
least one RXR-type retinoid receptor agonist into appropriate cosmetically/therapeutically
acceptable vehicle, diluent or carrier therefor, said at least one
agonist characteristically having the following structural formula
(I): ##STR3## in which Ar is one of the following radicals: ##STR4##
wherein the pentagonal heterocycles are substituted in position
4 or 5; A is --(CH.sub.2).sub.n wherein n ranges from 0 to 5; B
is a --COOH radical or a radical --COOR.sub.7, --CONR.sub.8 R.sub.9,
--CH.sub.2 OH, --CH.sub.2 OR.sub.10, --CH.sub.2 OCOR.sub.10, --CHO,
--CH(OR.sub.11).sub.2, --CHOR.sub.12 O, --COR.sub.6, --CR.sub.6
(OR.sub.11).sub.2 or --CR.sub.6 OR.sub.12 O; X is an oxygen atom,
the radical --C--(R.sub.5).sub.2 or the radical S(O).sub.m wherein
m is 0, 1 or 2; R.sub.1 is a halogen atom or an alkyl radical having
from 1 to 6 carbon atoms; R.sub.2 is a hydrogen atom or an alkyl
radical having from 1 to 6 carbon atoms or a halogen atom; the radicals
R.sub.3, which may be identical or different, are each an alkyl
radical having from 1 to 6 carbon atoms, a halogen atom or a radical
--OR.sub.10, --SR.sub.10, --OCOR.sub.10, --SCOR.sub.10, --NH.sub.2,
--NHR.sub.10, --N(R.sub.10).sub.2, --NHCOR.sub.10 or --NR.sub.10
COR.sub.10 ; the radicals R.sub.4, which may be identical or different,
are each a hydrogen atom, an alkyl radical having from 1 to 6 carbon
atoms, a halogen atom, an alkoxy radical having from 1 to 6 carbon
atoms or a thioalkoxy radical having from 1 to 6 carbon atoms; the
radicals R.sub.5, which may be identical or different, are each
a hydrogen atom or an alkyl radical having from 1 to 6 carbon atoms;
R.sub.6 is an alkyl radical having from 1 to 6 carbon atoms, a cycloalkyl
radical having from 3 to 6 carbon atoms or an alkenyl radical having
from 2 to 6 carbon atoms; R.sub.7 is an alkyl radical having from
1 to 10 carbon atoms, a cycloalkyl radical having from 5 to 10 carbon
atoms or a phenyl or lower alkylphenyl radical; the radicals R.sub.8
and R.sub.9, which may be identical or different, are each a hydrogen
atom, an alkyl radical having from 1 to 10 carbon atoms, a cycloalkyl
radical having from 5 to 10 carbon atoms, a phenyl radical or a
lower alkylphenyl radical; the radicals R.sub.10 which may be identical
or different, are each an alkyl radical having from 1 to 10 carbon
atoms, a phenyl radical or a lower alkylphenyl radical; R.sub.11
is an alkyl radical having from 1 to 6 carbon atoms; and R.sub.12
is a divalent alkylene radical having from 2 to 5 carbon atoms;
or the optical and/or geometrical isomers, acyl derivatives or pharmaceutically
acceptable salts thereof, either singly or in any admixture.
The subject compounds are useful active principles for inducing
and/or stimulating hair growth and/or retarding hair loss.
The compounds of formula I are described, in particular, in WO-A-94/17,796
and recognized for their agonist property with respect to RXR-type
retinoid receptors.
In a preferred embodiment of the invention, the halogen atom may
be a chlorine, bromine, fluorine or iodine atom, more preferably
a chlorine, bromine or iodine atom.
In another preferred embodiment of the invention, R.sub.1 is an
alkyl radical having from 1 to 6 carbon atoms, and even more preferably
R.sub.1 is a methyl radical.
In another preferred embodiment of the invention, R.sub.2 is a
hydrogen atom or an alkyl radical having from 1 to 6 carbon atoms,
and even more preferably R.sub.2 is a hydrogen atom.
In yet another preferred embodiment of the invention, R.sub.3 is
an alkyl radical having from 1 to 6 carbon atoms, and even more
preferably R.sub.3 is a methyl radical.
In still another preferred embodiment of the invention, R.sub.4
is a hydrogen atom or an alkyl radical having from 1 to 6 carbon
atoms, and even more preferably R.sub.4 is a hydrogen atom.
In still another preferred embodiment of the invention, R.sub.5
is an alkyl radical having from 1 to 6 carbon atoms, and even more
preferably R.sub.5 is a methyl radical.
And, in yet another preferred embodiment of the invention, --A--B--
is a radical --(CH.sub.2).sub.n --COOR.sub.7, or a radical --(CH.sub.2).sub.n
--CONR.sub.8 R.sub.9, (R.sub.7, R.sub.8 and R.sub.9 being defined
as above) and, preferably, n is equal to zero and B is a radical
--COOR.sub.7.
The compounds according to the invention are preferably selected
from among:
2-[(E)-2-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)propen-1-yl]-
4-thiophenecarboxylic acid;
2-[(E)-2-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)propen-1-yl]-
5-thiophenecarboxylic acid;
2-[(E)-2-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethylnaphthalen-2-yl)propen-1-
yl]-4-furancarboxylic acid;
4-[(E)-2-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)propen-1-yl]b
enzoic acid;
2-[(E)-2-(4,4,7-trimethyl-6-thiochromanyl)propen-1-yl]-4-thiophenecarboxyli
c acid;
ethyl 2-[(E)-2-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)propen-1-yl]
-4-thiophenecarboxylate;
2-[(E)-2-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)propen-1-yl]-
4-thiazolecarboxylic acid;
2-[(E)-2-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)propen-1-yl]-
5-imidazolecarboxylic acid.
A more preferred compound is 2-[(E)-2-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)propen-1-yl]
-4-thiophenecarboxylic azid.
These compounds may be used alone or as a mixture.
The "effective amount" of compound used obviously corresponds
to the amount required to elicit the desired effect. One skilled
in this art can readily determine this effective amount, which depends
upon the nature of the compound and upon the individual thus treated.
To provide an order of magnitude, in the compositions according
to the invention, the agonist compound is advantageously present
in a concentration of from 0.001% to 10% by weight relative to the
total weight of the composition and preferably from 0.01% to 1%.
The physiologically acceptable medium in which the active agent
is formulated according to the invention is either anhydrous or
aqueous. By the expression "anhydrous medium" is intended
a solvent medium containing less than 1% of water. This medium comprises
a solvent or mixture of solvents selected, more particularly, from
among C.sub.2 -C.sub.4 lower alcohols such as ethyl alcohol, alkylene
glycols such as propylene glycol, alkylene glycol alkyl ethers or
dialkylene glycol alkyl ethers in which the alkyl or alkylene radicals
have from 1 to 6 carbon atoms. By the expression "aqueous medium"
is intended a medium comprising water or a mixture of water and
another physiologically acceptable solvent selected, in particular,
from among the organic solvents indicated above. In the latter case,
when they are present, these other solvents constitute approximately
5% to 95% of the weight of the composition.
The physiologically acceptable medium (vehicle, carrier or diluent)
may contain other adjuvants and additives usually used in the cosmetic
or pharmaceutical field, such as surfactants, thickeners, gelling
agents, cosmetic agents, preservatives, and basifying or acidifying
agents well known to this art, and in amounts which are sufficient
to obtain the desired presentation form, in particular a relatively
thickened lotion, a gel, an emulsion or a cream. The composition
may optionally be in a form which is pressurized as an aerosol or
vaporized from a pump-dispenser bottle.
It is also envisaged to include, in admixture with the active agent,
compounds which further improve the activity in respect of regrowth
of the hair and/or retarding hair loss, and which are already known
for such activity.
Among the latter active species, particularly exemplary are:
(a) nicotinic acid esters including, in particular, tocopheryl
nicotinate, benzyl nicotinate and C.sub.1 -C.sub.6 alkyl nicotinates
such as methyl or hexyl nicotinate;
(b) pyrimidine derivatives such as 2,4-diamino-6-piperidinopyrimidine
3-oxide or "Minoxidil," described in U.S. Pat. Nos. 4,139,619
and 4,596,812;
(c) agents which promote regrowth of the hair, such as those described
in EP-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, Diltiazem, Nimodipine
and Nifedipine;
(f) hormones such as estriol or analogs thereof, and thyroxine
and its salts;
(g) steroidal anti-inflammatory agents such as corticosteroids
(for example hydrocortisone);
(h) antiandrogens such as oxendolone, spironolactone, diethylstilbestrol
and flutamide;
(i) steroidal or non-steroidal 5-.alpha.-reductase inhibitors such
as finasteride;
(j) potassium agonists such as cromakalim and nicorandil.
Other such compounds include, for example, Diazoxide, Spiroxazone,
phospholipids such as lecithin, linoleic and linolenic acids, salicylic
acid and its derivatives described in FR-2,581,542, such as salicylic
acid derivatives bearing an alkanoyl radical having from 2 to 12
carbon atoms in position 5 on the benzene ring, hydroxycarboxylic
or ketocarboxylic acids and their esters, lactones and their corresponding
salts, anthralin, carotenoids, eicosatetraynoic and eicosatriynoic
acids or their esters and amides, vitamin D and derivatives thereof,
and extracts of plant or bacterial origin.
The compositions comprising at least one compound of formula (I)
may be in liposomal form, as described, in particular, in WO-94/22,468,
filed Oct. 13, 1994 by Anti-Cancer Inc. Thus, the compound encapsulated
in the liposomes may be delivered selectively to the hair follicle.
The pharmaceutical compositions according to the invention may
be administered parenterally, enterally or topically. The pharmaceutical
composition is preferably administered topically.
The cosmetic compositions according to the invention are topically
applied to the alopecic areas of the scalp and the hair of an individual,
and are optionally maintained in contact for several hours and,
optionally, are then rinsed out. It is possible, for example, to
apply a composition containing an effective amount of at least one
compound of formula (I) in the evening, to maintain the composition
in contact overnight and optionally to shampoo out in the morning.
These applications may be repeated daily for one or more months
according to the individual.
Thus, the present invention also features a regime or regimen for
the cosmetic treatment of the hair and/or the scalp, comprising
topically applying thereto a cosmetic composition which comprises
an effective amount of at least one compound of formula (I) to the
hair and/or the scalp, maintaining this composition in contact with
the hair and/or the scalp and, optionally, rinsing same therefrom.
Such treatment presents the advantages of a cosmetic technique,
insofar as it permits the beauty of the hair to be enhanced while
at the same lime imparting greater vigor and an improved appearance
thereto.
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.
EXAMPLE 1
Determination of the Effect of (E)-2-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)propen-1-yl]-4
-thiorhenecarboxylic Acid on the Lengthening and Survival Time of
Hair Follicles Maintained in Vitro:
Hair follicles viable in vitro were prepared according to the technique
described in French patent application No. 95/08,465, filed Jul.
12, 1995 and assigned to the assignee hereof.
From a scalp biopsy, a relatively thin strip of scalp was isolated
using a scalpel. The adipose tissue surrounding the follicles was
removed using microtweezers, taking care not to damage the hair
bulb. Under a microscope, the follicle was dissected with a scalpel
in order to separate it from its epidermal and dermal environment.
The follicles were then cultured in the wells of Costar-type 24-well
plates, at a rate of one follicle per well. Each well contained
0.5 ml of Williams E medium supplemented with penicillin and streptomycin
to a final concentration of 50 IU/ml, glutamine to 2 mM, bovine
insulin to 0.01 mg/ml and hydrocortisone to 0.04 .mu.g/ml.
The follicles were then measured using a microscope fitted with
a micrometric eyepiece.
The follicles were remeasured after 24 hours and those whose lengthening
was less than 0.3 graduations of the micrometer, corresponding to
0.16 mm, were discarded.
The follicles retained for the experiment were then cultured in
Williams E medium containing or not containing (E)-2-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)propen-1-yl]-4
-thiophenecarboxylic acid.
Condition A: complete Williams E medium without the acid:
Condition B: complete Williams E medium+the acid at a concentration
of 10.sup.-8 M.
Results:
______________________________________ Average Standard Days lengthening
deviation n % survival ______________________________________ Condition
A: 0 0.00 0.00 11 100 3 0.96 0.14 11 100 4 1.22 0.20 11 100 5 1.48
0.24 11 100 6 1.64 0.28 11 100 7 1.85 0.32 11 100 10 2.72 0.34 8
73 11 2.97 0.43 8 73 12 3.20 0.49 8 73 13 3.47 0.58 8 73 14 3.76
0.62 8 73 19 4.89 0.99 8 73 21 5.55 0.95 8 73 26 5.75 0.88 8 73
27 nd -- 5 45 28 nd -- 4 36 31 nd -- 3 27 34 nd -- 3 27 35 nd --
0 0 Condition B: 0 0.00 0.00 12 100 3 1.18 0.07 12 100 4 1.47 0.08
12 100 5 1.75 0.13 12 100 6 2.04 0.18 12 100 7 2.29 0.26 12 100
10 3.30 0.42 11 92 11 3.60 0.46 11 92 12 4.06 0.29 10 83 13 4.53
0.41 10 83 14 4.85 0.44 10 83 19 6.80 0.36 9 75 21 7.54 0.33 9 75
26 nd -- 8 67 27 nd -- 8 67 28 nd -- 8 67 31 nd -- 7 58 34 nd --
4 33 35 nd -- 0 0 ______________________________________
These results demonstrate that (E)-2-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)propen-1-yl]-4
-thiophenecarboxylic acid promoted lengthening of the hair follicle
in culture and increased its survival time. The increase in survival
time corresponds to an increase in the duration of the phase of
the cycle in which hair was found and thus made it possible to delay
its loss.
EXAMPLE 2
In this example, specific compositions according to the invention
were formulated:
These compositions were formulated according to conventional techniques
in the cosmetics or pharmacy arts.
______________________________________ Lotion to combat hair loss:
______________________________________ Compound of formula 1 0.20
g Propylene glycol 10.00 g Isopropyl alcohol qs 100.00 g ______________________________________
1 ml of this lotion was applied to the scalp, at a frequency of
once or twice a day.
______________________________________ Lotion to combat hair loss:
______________________________________ Compound of formula 1 0.01
g Propylene glycol 30.00 g Ethyl alcohol 40.05 g Water qs 100.00
g ______________________________________
This lotion was applied to the scalp once or twice a day at a rate
of 1 ml per application.
______________________________________ Thickened lotion for combating
hair loss: ______________________________________ Compound of formula
1 0.20 g Kawaine 2.00 g Hydroxypropylcellulose marketed by Hercules
under the trademark Klucel G 3.50 g Ethyl alcohol qs 100.00 g ______________________________________
This thickened lotion was applied to the scalp once or twice a
day at a rate of 1 ml per application.
______________________________________ Lotion to combat hair loss:
______________________________________ Compound of formula 1 0.05
g Propylene glycol monomethyl ether marketed under the trademark
Dowanol PM by Dow Chemical 20.00 g Hydroxypropylcellulose marketed
by Hercules under the trademark Klucel G 3.00 g Ethyl alcohol 40.00
g Water qs 100.00 g ______________________________________
This thickened lotion was applied to the scalp once or twice a
day at a rate of 1 ml per application.
While the invention has been described in terms of various preferred
embodiments, the skilled artisan will appreciate that various modifications,
substitutions, omissions, and changes may be made without departing
from the spirit thereof. Accordingly, it is intended that the scope
of the present invention be limited solely by the scope of the following
claims, including equivalents thereof. |