Hair loss abstract
Topically applicable hair growth-/hair loss-affecting cosmetic/therapeutic
compositions are disclosed for treating mammalian subjects with
hair or scalp disorders comprising an effective amount of at least
one .alpha.-pyrone compound as kavain, formulated into a physiologically
topically acceptable carrier medium, whether organic or aqueous,
or mixtures thereof.
Hair loss claims
What is claimed is:
1. A topically applicable hair growth-/hair loss-affecting composition
of matter, comprising a hair growth stimulating and/or hair loss
retarding effective amount of at least one .alpha.-pyrone compound
having the structural formula: ##STR2## in which R.sub.1 is a hydrogen
atom or an alkoxy radical having from 1 to 4 carbon atoms, R.sub.2
is a hydrogen atom or a hydroxyl group, and R.sub.3 is an alkyl
radical having from 1 to 4 carbon atoms or a styryl or phenethyl
radical optionally substituted by one or two methylenedioxy radicals
or one or two hydroxyl groups and/or one or two alkoxy radicals
having from 1 to 4 carbon atoms, with the proviso that, when R.sub.2
is a hydroxyl group, then R.sub.3 is necessarily an unsubstituted
phenethyl radical, with the further proviso that when R.sub.3 is
an alkyl radical having 1 to 4 carbon atoms, then R.sub.1 and R.sub.2
cannot both be hydrogen, in a physiologically topically acceptable
carrier medium.
2. The topical composition as defined by claim 1, wherein said
.alpha.-pyrone compound is kavain.
3. The topical composition as defined by claim 1, wherein said
.alpha.-pyrone compound is 5,6-dehydrokavain.
4. The topical composition as defined by claim 1, wherein said
.alpha.-pyrone compound is 7,8-dihydrokavain.
5. The topical composition as defined by claim 1, wherein said
.alpha.-pyrone compound is dihydrokavain-5-ol.
6. The topical composition as defined by claim 1, wherein said
.alpha.-pyrone compound is methysticin.
7. The topical composition as defined by claim 1, wherein said
.alpha.-pyrone compound is 7,8-dihydromethysticin.
8. The topical composition as defined by claim 1, wherein said
.alpha.-pyrone compound is yangonin.
9. The topical composition as defined by claim 1, wherein said
.alpha.-pyrone compound is noryangonin.
10. The topical composition as defined by claim 1, wherein said
.alpha.-pyrone compound is 11-methoxynoryangonin.
11. The topical composition as defined by claim 1, wherein said
.alpha.-pyrone compound is 11-methoxyyangonin.
12. The topical composition as defined by claim 1, wherein said
.alpha.-pyrone compound is 7,8-dihydroyangonin.
13. The topical composition as defined by claim 1, comprising from
about 0.05% to about 10% by weight of said at least one .alpha.-pyrone
compound.
14. The topical composition as defined by claim 13, comprising
from about 0.1% to about 6% by weight of said at least one .alpha.-pyrone
compound.
15. The topical composition as defined by claim 1, said physiologically
topically acceptable carrier medium comprising an anhydrous organic
solvent medium.
16. The topical composition as defined by claim 15, said anhydrous
organic solvent medium comprising a lower alcohol, an alkylene glycol,
an alkylene glycol or dialkylene glycol alkyl ether, or mixture
thereof.
17. The topical composition as defined by claim 1, said physiologically
topically acceptable carrier medium comprising an aqueous medium.
18. The topical composition as defined by claim 17, said aqueous
medium also comprising from 5% to 95% by weight of an organic solvent.
19. The topical composition as defined by claim 1, further comprising
at least one conventional cosmetic/pharmaceutical additive or adjuvant.
20. The topical composition as defined by claim 19 comprising at
least one surfactant, thickening agent, gelling agent, cosmetically
active agent, preservative, alkalinizing agent or acidifying agent.
21. The topical composition as defined by claim 19, comprising
from about 0.1% to 6% by weight of a thickening agent.
22. The topical composition as defined by claim 1, having a pH
ranging from 3 to 9.
23. The topical composition as defined by claim 22, having a pH
ranging from 5 to 8.
24. The topical composition as defined by claim 1, further comprising
at least one hair growth-/hair loss-affecting active agent wherein
said agent is a nicotinic acid ester.
25. The topical composition as defined by claim 1, comprising a
lotion, cream, gel, emulsion, ointment, salve, or shampoo.
26. The topical composition as defined by claim 25, comprising
an aerosol or spray.
27. A topically applicable hair growth-/hair loss-affecting composition
of matter, consisting essentially of a hair growth stimulating and/or
hair loss retarding effective amount of at least one .alpha.-pyrone
compound having the structural formula: ##STR3## in which R.sub.1
is a hydrogen atom or an alkoxy radical having from 1 to 4 carbon
atoms, R.sub.2 is a hydrogen atom or a hydroxyl group, and R.sub.3
is an alkyl radical having from 1 to 4 carbon atoms or a styryl
or phenethyl radical optionally substituted by one or two methylenedioxy
radicals or one or two hydroxyl groups and/or one or two alkoxy
radicals having from 1 to 4 carbon atoms, with the proviso that,
when R.sub.2 is a hydroxyl group, then R.sub.3 is necessarily an
unsubstituted phenethyl radical, and with the further proviso that
if R.sub.3 is an alkyl radical having 1 to 4 carbon atoms, then
R.sub.1 and R.sub.2 cannot both be hydrogen, in a physiologically
topically acceptable carrier medium.
28. A method for inducing/stimulating hair growth and/or retarding
hair loss on a mammalian subject, comprising topically applying
to the hair and/or skin of said mammalian subject an effective amount
of the topical composition as defined by claim 1, for a time sufficient
to elicit said hair growth-/hair loss-affecting response.
29. The method as defined by claim 28, comprising topically applying
said composition to the hair or scalp of said mammalian subject,
for the therapeutic treatment of a disorder thereof.
Hair loss description
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to novel cosmetic and/or therapeutic
compositions for topical application to mammalian subjects, comprising
at least one .alpha.-pyrone as the active principle thereof, and
to the use of such novel compositions for inducing and stimulating
hair growth and/or retarding hair loss.
2. Description of the Prior Art
In human subjects hair growth and renewal are principally determined
by the activity of the hair follicles. This activity is cyclic and
essentially entails three phases, namely, the anagen phase, the
catagen phase and the telogen phase.
The active anagen phase, or growth phase, which lasts for several
years during which the hair elongates, is succeeded by a very short
and transient catagen phase and then a rest or quiescent phase,
designated the telogen phase, which lasts for a few months.
At the end of the rest period, the hairs are shed and another cycle
begins anew. The head of hair is hence being constantly renewed
and, of the approximately 150,000 hairs on a human head, approximately
10% are at rest at any given instant and thus will be replaced in
a few months.
In a large number of cases, early hair loss occurs in genetically
predisposed subjects, and it affects men in particular. This applies,
more especially, to androgenetic or androgenic or, alternatively,
androgeno-genetic alopecia.
This alopecia is essentially due to a disturbance of hair renewal,
which initially gives rise to an acceleration of the frequency of
the cycles at the expense of the quality of the hairs, and then
of their quantity. There is a gradual depletion of the head of hair
through regression of so-called "terminal" hairs at the
down stage. Some regions are affected preferentially, in particular
the temporal or frontal areas in men, and a diffuse alopecia of
the crown is observed in women.
Compositions that eliminate or reduce the effects of androgenetic
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
have been suggested for such purposes, for example, 6-amino-1,2-dihydro-1-hydroxy-2-imino-4-piperidinopyrimidine
and derivatives thereof, as described, more especially, 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.
SUMMARY OF THE INVENTION
Accordingly, a major object of the present invention is the provision
of compounds of the .alpha.-pyrone type for efficaciously inducing/stimulating
hair growth and/or decreasing hair loss.
Briefly, the present invention features novel cosmetic and/or therapeutic
compositions for inducing and stimulating hair growth and/or retarding
hair loss, comprising, in a physiologically acceptable medium, at
least one .alpha.-pyrone having the following structural formula:
##STR1## in which R.sub.1 is a hydrogen atom or an alkoxy radical
having from 1 to 4 carbon atoms; R.sub.2 is a hydrogen atom or a
hydroxyl group; and R.sub.3 is an alkyl radical having from 1 to
4 carbon atoms or a styryl or phenethyl radical optionally substituted
by one or two methylenedioxy radicals or one or two hydroxyl groups
and/or one or two alkoxy radicals having from 1 to 4 carbon atoms,
with the proviso that, when R.sub.2 is a hydroxyl group, then R.sub.3
is necessarily an unsubstituted phenethyl radical.
DETAILED DESCRIPTION OF BEST MODE AND PREFERRED EMBODIMENTS OF
THE INVENTION
More particularly, according to the present invention, it will
be appreciated that the .alpha.-pyrone(s) comprising the subject
compositions contain(s) either single- or one or two double-bonds.
The present invention also features topical application of the
subject cosmetic/therapeutic compositions for inducing/stimulating
hair growth and/or for preventing/retarding hair loss.
Among the .alpha.-pyrone compounds comprising the cosmetic/therapeutic
compositions of the invention, preferred are those in which:
(i) R.sub.1 and R.sub.2 are hydrogen atoms and R.sub.3 is a methyl
radical, namely, parasorbic acid, also known as parasorbinic acid,
or 5,6-dihydro-6-methyl-2H-pyran-2-one;
(ii) R.sub.1 and R.sub.2 are hydrogen atoms and R.sub.3 is a methyl
radical, namely, 5-methyl-.delta.-valerolactone or tetrahydro-6-methyl-2H-pyran-2-one;
(iii) R.sub.1 is a methoxy radical, R.sub.2 is a hydrogen atom
and R.sub.3 is a styryl radical, namely, kavain or 5,6-dihydro-4-methoxy-6-(2-phenylethenyl)-2H-pyran-2one;
(iv) R.sub.1 is a methoxy radical, R.sub.2 is a hydrogen atom and
R.sub.3 is a styryl radical, namely, 5,6-dehydrokavain or 4-methoxy-6-(2-phenylethenyl)-2H-pyran-2-one;
(v) R.sub.1 is a methoxy radical, R.sub.2 is a hydrogen atom and
R.sub.3 is a phenethyl radical, namely, 7,8-dihydrokavain or marindinin
or 5,6-dihydro-4-methoxy-6-(2-phenylethyl)-2H-pyran-2-one;
(vi) R.sub.1 is a methoxy radical, R.sub.2 is a hydroxyl group
and R.sub.3 is a phenethyl radical, namely, dihydrokavain-5-ol or
5,6-dihydro-5-hydroxy-4-methoxy-6-(2-phenylethyl)-2H-pyran-2-one;
(vii) R.sub.1 is a methoxy radical, R.sub.2 is a hydrogen atom
and R.sub.3 is a 3,4-methylenedioxystyryl radical, namely, methysticin
or 6-[2-(1,3-benzodioxol-5-yl)ethenyl]-5,6-dihydro-4-methoxy-2H-pyran-2-one;
(viii) R.sub.1 is a methoxy radical, R.sub.2 is a hydrogen atom
and R.sub.3 is a 3,4-methylenedioxyphenethyl radical, namely, 7,8-dihydromethysticin
or 6-[2-(1,3-benzodioxol-5-yl)ethyl]-5,6-dihydro-4-methoxy-2H-pyran-2-one;
(ix) R.sub.1 is a methoxy radical, R.sub.2 is a hydrogen atom and
R.sub.3 is a 4-methoxystyryl radical, namely, yangonin or 4-methoxy-6-[2-methoxyphenyl)ethenyl]-2H-pyran-2-one;
(x) R.sub.1 is a methoxy radical, R.sub.2 is a hydrogen atom and
R.sub.3 is a 4-hydroxystyryl radical, namely, noryangonin or 6-[2-(4-hydroxyphenyl)ethenyl]-4-methoxy-2H-pyran-2-one;
(xi) R.sub.1 is a methoxy radical, R.sub.2 is a hydrogen atom and
R.sub.3 is a 4-hydroxy-3-methoxystyryl radical, namely, 11-methoxynoryangonin
or 6-[2-(4-hydroxy-3-methoxyphenyl)ethenyl]-4-methoxy-2H-pyran-2-one;
(xii) R.sub.1 is a methoxy radical, R.sub.2 is a hydrogen atom
and R.sub.3 is a 3,4-dimethoxystyryl radical, namely, 11-methoxyyangonin
or 6-[2-(3,4-dimethoxyphenyl)ethenyl]-4-methoxy-2H-pyran-2-one;
(xiii) R.sub.1 is a methoxy radical, R.sub.2 is a hydrogen atom
and R.sub.3 is a 4-methoxyphenethyl radical, namely, 7,8-dihydroyangonin
or 4-methoxy-6-[2-(4methoxyphenyl)ethyl]-2H-pyran-2-one.
According to the present invention, 5-methyl-.delta.-valerolactone
and kavain are the most preferred compounds.
The .alpha.-pyrone compounds having the structural formula given
above are preferably employed in proportions ranging from approximately
0.05% to 10% by weight, and more preferably from 0.1% to 6% by weight,
relative to the total weight of the composition.
All of these .alpha.-pyrone compounds are per se well known to
this art.
Kavain and its derivatives, methysticin and its derivatives and
yangonin and its derivatives are present in the natural state in
the Polynesian plant Piper Methysticum or Kawa-kawa; parasorbic
acid is, in particular, present in Sorbus Aucuparia berries; and
5-methyl-.delta.-valerolactone is, in particular, present in Avena
Sativa. They may be extracted from these various sources via any
one of a number of well-known extraction techniques.
These compounds may also be synthesized according to a variety
of processes described in the literature.
Thus, kavain and derivatives thereof can be prepared via the processes
described in Fowler et al, J. Chem. Soc., 3642 (1950); T. Isawa
et al, Chem. Lett., 161 (1975); Z. H. Israili et al, J. Org. Chem.,
41, 4070 (1976); S. Castellino et al, Tetrahedron Lett., 25, 4059
(1984); A. Belanger et al, Can. J. Chem., 53, 201 (1975); E. Susuki
et al, Synthesis, 192 (1975); H. Achenbach et al, Tetrahedron Lett.,
3259 (1970) and 119 (1974); R. Haensel et al, Chem. Ber., 106, 570
(1973).
Other of these compounds can be prepared via the processes described
in the following publications:
(a) Methysticin and derivatives thereof: M. W. Klohs et al, J.
Org. Chem., 24, 1829 (1959);
(b) Yangonin and derivatives thereof: T. M. Harris et al, J. Org.
Chem., 33, 2399 (1968); E. Hipolito et al, Rev. Latinoam. Quim.,
8, 79 (1977);
(c) Parasorbic acid: L. J. Haynes et al, J. Chem. Soc., 954 (1946);
T. Sato, Heterocycles, 24, 2173 (1986); R. Stevenson et al, J. Nat.
Prod. (Lloydia), 51, 1215 (1988); A. S. Gopalan et al, Tetrahedron
Lett., 31, 5575 (1990);
(d) 5-Methyl-.delta.-valerolactone: T. H. Parliment et al, Chem.
Ind. (London), 1845 (1966); D. Taub et al, Tetrahedron, 24, 2443
(1968); G. Sturtz et al, Tetrahedron Lett., 47 (1976); D. Seebach
et al, Helv. Chim. Acta, 698, 2342 (1985); B. Giese et al, J. Org.
Chem., 51, 3726 (1986).
The physiologically acceptable medium formulated into the compositions
according to the invention can be anhydrous or, to the contrary,
aqueous. By "anhydrous medium" is intended a solvent medium
containing less than 1% of water. This medium can essentially consist
of a solvent or a mixture of solvents selected, more especially,
from among 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 in which the alkyl or alkylene radicals
have from 1 to 4 carbon atoms. By "aqueous medium" is
intended a medium consisting of 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,
these other solvents, when present, constitute approximately 5%
to 95% by weight of the composition.
The subject compositions can contain other adjuvants and additives
typically employed in the cosmetic or pharmaceutical arts for the
purpose of providing topically applicable compositions, such as
surfactants, thickening or gelling agents, cosmetic agents, preservatives
and alkalinizing or acidifying agents which are well known to the
art, and in amounts sufficient to obtain the desired form of presentation,
in particular of a more or less thickened lotion, a gel, an ointment,
a salve, an emulsion or a cream. The composition can also, where
appropriate, be pressurized as an aerosol or vaporized from a pump
bottle.
When the composition is thickened or gelled using a thickening
agent, such thickening agent is generally present in concentrations
ranging from approximately 0.1% to 6% relative to the total weight
of the composition.
The subject compositions can be used, in particular, in treatments
employing an application, whether or not followed by a rinse, or,
alternatively, in the form of a shampoo.
The pH of the subject compositions advantageously ranges from approximately
3 to 9, and preferably from 5 to 8.
The compositions according to the invention can contain, other
than the .alpha.-pyrone, compounds which further improve or enhance
the activity in respect of hair regrowth and/or in respect of retarding
hair loss, and which are already known for such activity.
Exemplary such compounds include:
(a') nicotinic acid esters including, in particular, tocopherol
nicotinate, benzyl nicotinate and C.sub.1 -C.sub.6 alkyl nicotinates,
such as methyl or hexyl nicotinate;
(b') steroidal and non-steroidal anti-inflammatory agents, especially
hydrocortisone, its salts and derivatives thereof, niflumic acid,
and the like;
(c') retinoids such as all-trans-retinoic acid, also known as tretinoin,
isotretinoin, retinol or vitamin A, and derivatives thereof, for
example the acetate, palmitate or propionate, motretinide, etretinate
and zinc all-trans-retinoate;
(d') pyrimidine derivatives such as 6-amino-1,2-dihydro-1-hydroxy-2-imino-4-piperidinopyrimidine,
also known as "Minoxidil" as described in U.S Pat. No.
4,139,619;
(e') antibacterial agents such as macrolides, pyranosides and tetracyclines,
and erythromycin in particular;
(f') calcium antagonists such as cinnarizine and diltiazem;
(g') hormones such as oestriol or analogs thereof or thyroxine
and salts thereof;
(h') antiandrogens such as oxendolone, spironolactone and diethylstilbestrol;
(i') 5-.delta.-reductase inhibitors;
(j') OH radical trapping agents such as dimethyl sulfoxide.
Other such compounds include, for example, diazoxide, spiroxazone,
phospholipids such as lecithin, linoleic and linolenic acids, salicylic
acid and derivatives thereof described in FR-2,581,542, such as
salicylic acid derivatives bearing an alkanoyl substituent having
2 to 12 carbon atoms at position 5 of the benzene ring, hydroxycarboxylic
or ketocarboxylic acids and esters thereof, lactones and their corresponding
salts, anthralin, carotenoids, and icosatetraynoic and icosatriynoic
acids or the esters and amides thereof.
The regime for treating hair loss entails applying an effective
amount of a composition according to the invention to the alopecic
regions of an individual's scalp and hair, permitting it to remain
there for several hours and, where appropriate, in rinsing.
For example, such a composition can be applied to the hair and
scalp at night, kept there all night long and, where appropriate,
shampooed out in the morning. Alternatively, the hair may be washed
using this composition, and maintained in contact with the hair
and scalp for a few minutes before rinsing. These applications may
be repeated daily for one or several months, depending on the particular
individual.
The aforesaid regimes are also in the nature of a cosmetic treatment,
inasmuch as they improve the attractiveness of the hair by imparting
more bounce and a better appearance thereto.
The .alpha.-pyrones described above can also be used in formulations
for the treatment of scalp disorders such as alopecia.
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.
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