Hair loss abstract
A regimen for inducing/stimulating hair growth and/or retarding
hair loss on an individual in need of such treatment comprises topically
applying to the affected hair and/or scalp of such individual, a
hair growth stimulating and/or hair loss retarding effective amount
of at least one 2,3-dihydroxypropyl-2-(1-oxohydrocarbyl) amino-2-deoxyglucopyranoside
having the structural formula: ##STR1## in which R is a linear or
branched, saturated or unsaturated hydrocarbon radical having from
5 to 21 carbon atoms.
Hair loss claims
What is claimed is:
1. A method for inducing/stimulating hair growth or retarding hair
loss or both inducing/stimulating hair growth and retarding hair
loss on a mammalian subject in need of such treatment, comprising
topically applying to the affected hair or scalp of said mammalian
subject a hair growth stimulating or hair loss retarding effective
amount of at least one 2,3-dihydroxypropyl-2-(1-oxohydrocarbyl)
amino-2-deoxyglucopyranoside having the structural formula: ##STR5##
in which R is a linear or branched, saturated or unsaturated hydrocarbon
radical having from 5 to 21 carbon atoms.
2. The method as defined by claim 1, wherein said structural formula
R is a hydrocarbon radical having from 7 to 17 carbon atoms.
3. The method as defined by claim 2, wherein said structural formula
R is a hydrocarbon radical having from 7 to 13 carbon atoms.
4. The method as defined by claim 1, wherein said at least one
2-deoxyglucopyranoside is 2,3-dihydroxypropyl-2-(1-oxo-10-undecenyl)-amino-2-deoxyglucopyranoside.
5. The method as defined by claim 1, comprising topically applying
said at least one 2-deoxyglucopyranoside to an alopecic area of
the scalp of a human subject.
6. The method as defined by claim 1, comprising topically applying
said at least one 2-deoxyglucopyranoside to the wet hair of a human
subject.
7. The method as defined by claim 1, comprising maintaining said
at least one 2-deoxyglucopyranoside in contact with said affected
hair or scalp or both for at least 2 minutes.
8. The method as defined by claim 1, comprising maintaining said
at least one 2-deoxyglucopyranoside in contact with said affected
hair or scalp or both for at least 5 minutes.
Hair loss description
BACKGROUND OF THE INVENTION
1. Technical Field of the Invention
The present invention relates to novel cosmetic and/or therapeutic
compositions for topical application to mammalian subjects which
are intended to induce and stimulate hair growth and/or to slow
down or retard hair loss.
2. Description of the Prior Art
In human subjects, hair growth and hair renewal are principally
determined by the activity of the hair follicles. This activity
is cyclic and essentially entails three phases, namely, the anagenic,
catagenic and telogenic phases. The anagenic active phase, or growth
phase, which lasts for several years and during which the hair elongates,
is followed by a transitional catagenic phase of about two weeks,
during which the follicle regresses and becomes involuted, after
which there is a rest phase or telogenic phase which lasts about
70 days, at the end of which the hair falls out. Following this,
another cycle begins. The follicles are genetically programmed to
produce about 25 regrowths, and a normal cycle lasts on average
for five years, thereby permitting permanent renewal of the head
of hair during a lifetime. Out of the approximately 150,000 hairs
which make up a head of hair, usually about 80 thus fall out each
day, which will be replaced in a few months.
Early thinning of the head of hair, or alopecia, which occurs in
certain individuals, has both genetic and hormonal implications.
The genetic aspect is seen when it corresponds to the "bald
nature" which is transmitted from father to son, and more rarely
from mother to son, and is very probably carried by several genes.
The hormonal aspect is seen when it is due to binding to molecular
receptors in the root of certain enzymatic degradation products
of testosterone, the principal male hormone, these aspects developing,
for example, following stress. This results in an accumulation of
collagen in the collective sheath (fibrosis), leading to a slowing-down
in the growth of the hair, and later its death. The disturbances
in hair renewal are reflected, in a first stage, by acceleration
of the frequency of the cycles, at the expense of the quality of
the hair and then of the amount thereof: there is gradual thinning
of the head of hair by regression of the so-called "end"
hairs at the duvet stage, and finally the moment is reached at which
there is no further regrowth. In men, the areas affected are principally
the temporal or frontal areas and the occipital region. In women,
diffuse alopecia of the vertex is observed.
More than 11 million men in France alone are directly affected
by hair loss. Thus, compounds and compositions which make it possible
to eliminate or reduce the effect of alopecia, and especially of
inducing or stimulating hair growth or of decreasing hair loss,
have long been sought in the cosmetic and pharmaceutical industries.
In approaches featuring a carbohydrate base, the synergistic action
of mono-, di- and oligosaccharides with various active agents has
recently been described; for example fructose in combination with
polyvinylpyrrolidone (see JP-08,040,846), trehalose with chitosan
and various natural active agents (see JP-08,020,514), the hydrolysis
products of alginic acid with a blood circulation accelerator and
a cell activator (see WO-96/07393), starch in combination with zinc
oxide and boric acid (see WO-95/35086), and glucose or fructose
in combination with globular cereal proteins or hydrolyzates thereof
(see FR-27/04751).
Oligosaccharides containing at least one disaccharide structural
unit comprising a uronic residue and a hexosamine residue (see EP-211,610)
have also been described.
Aldonolactones or hexosaccharic acids too have been described,
for example D-fucono-1,5-lactone (see EP-531,111), lactam forms
of saccharides, for example L-arabino-1,5-lactam and D-glucurono-6,3-lactam
(see EP-0,334,586), a cellobione/lactone polymer obtained via its
derivation into N-p-vinyl benzyl D-cellobionamide (see JP-05,043,418).
Glycosides of ergosterol (see JP-07,101,835 and JP-07,109,293),
of stigmasterol (see JP-07,138,181), of stigmastanol (see JP-07,109,294)
and p-.beta.-D-glucopyranosyloxycinnamic acid (see JP-07,258,042)
or glucosides derived from saponins (see WO-94/06402) are also known
to this art.
Only rarely do structures result from the grafting of an alkyl
chain onto a polyol. However, monopentadecanoylglycerol (see Yokoyama
Daisaburo, Yukagaku 1995, 44 (4) 266-73), polyalcohol glyceryl ethers,
in particular those obtained by condensation of pentaerythritol
with pentadecyl glycidyl ether (see JP-08,157,331) and, more particularly,
for carbohydrate-derived structures, undecylenyl trehalose (see
JP-08,053,326) and alkylpolyglycosides and/or O-acyl glucose derivatives
(see WO-93/02657) corresponding to the structure: ##STR2## in which
R.sub.1 is a radical or a mixture of alkyl or alkenyl radicals and/or
has the structure: ##STR3## in which R.sub.2 is a linear hydrocarbon
chain and R.sub.3 is hydrogen or a lower C.sub.1 -C.sub.4 alkyl
group, have indeed been described. All of these structures, which
are carbohydrate-based, differ from those of the invention, hereinbelow
more fully described.
Minoxidil.RTM. and Aminexil.RTM. are also known agents for improving
the condition of the hair. Minoxidil, or diamino-2,4-piperidono-6-pyrimidine-3-oxide
and derivatives thereof (see U.S. Pat. Nos. 3,461,461, 3,973,061,
3,464,987 and 4,139,619), which are molecules initially known for
their anti-hypertensive activity, have also proven to be active
in the treatment of hair loss. They stimulate division of the cells
which constitute the hair, promote vascularization of the root and,
lastly, retard the fibrosis and atrophy of the hair root.
However, although Minoxidil.RTM. diminishes hair loss in one-third
of patients and effects a slight amount of hair regrowth in another
third, it remains ineffective on the other individuals treated.
When applied morning and evening in the form of a lotion, it occasionally
entails side effects, such as palpitations, a lowering of blood
pressure or eczema. Moreover, the hair becomes greasy over the course
of this generally permanent treatment.
Aminexil.RTM., which is similar in structure to Minoxidil.RTM.
(see WO 96/09048), is diamino-2,4-pyrimidine-3-oxide, a molecule
capable of combating the production of the principal enzyme responsible
for fibrosis. However, this cosmetic compound unfortunately does
not act on the other causes of alopecia, namely, the hormonal and
vascular factors, which limits its field of application to a fraction
of the individuals afflicted with alopecia.
Thus, serious need continues to exist in this art for yet other
active compounds for stimulating/inducing hair growth and/or retarding
hair loss.
In addition, compounds of the type 2,3-dihydroxypropyl-2-(1-oxoalkyl)
amino-2-deoxyglucopyranoside have been formulated into washing compositions
for the hair, in particular those having anti-dandruff and hair-conditioning
properties (see FR-95/12215).
SUMMARY OF THE INVENTION
It has now unexpectedly and surprisingly been determined that certain
deoxyglucopyranoside compounds are conspicuously useful for inducing/stimulating
hair growth and/or reducing hair loss in individuals suffering from
alopecia.
Briefly, the present invention thus features inducing and stimulating
hair growth and/or reducing hair loss, by topically applying to
wet hair and to the alopecic regions of the scalp, for periods longer
than 2 minutes and preferably longer than 5 minutes, lotions based
on 2,3-dihydroxypropyl 2-(1-oxohydrocarbyl)amino-2-deoxyglucopyranoside,
the glucopyranoside content of which ranges from 0.1% to 30%.
DETAILED DESCRIPTION OF BEST MODE AND SPECIFIC/PREFERRED EMBODIMENTS
OF THE INVENTION
More particularly according to the present invention, the lotions
having a low content in active principle are applied without rinsing
or with rinsing with water after several hours. The lotions of high
concentration are maintained in contact for a few minutes and then
removed by rinsing. The applications are daily or twice-daily, the
treatment lasting, for average cases, from three to six months;
for more severe cases, under the observation of the patient or of
the haircare specialist, the treatment may be daily and for life.
The subject compositions do not cause any irritation of the scalp,
even after prolonged contact without rinsing.
The active principle of the aforesaid lotions is a compound having
the structural formula: ##STR4## in which R is a linear or branched,
saturated or unsaturated hydrocarbon radical having 5-21 carbon
atoms, and more particularly 7 to 13 carbon atoms. The 2,3-dihydroxypropyl
2-(1-oxo-10-undecenyl)amino-2-deoxyglucopyranoside derivative is
a preferred compound. The synthesis of these compounds is described
in French patent application No. 95/12215.
Thus, the present invention also features aqueous/alcoholic lotions
containing at least one of the above indicated glucopyranosides,
the glucopyranoside constituting 0.1% to 30% by weight relative
to the total weight of the composition, more preferably 0.1% to
15%, and even more preferably from 0.25% to 10% for the leave-in
compositions, and 2% to 30%, preferably 3% to 15% for the rinse-out
compositions. The pH of these compositions advantageously ranges
from 3 to 9 and preferably from 4.5 to 7.5.
The aqueous/alcoholic solvents advantageously constitute from 5
to 95% by weight relative to the total weight of the subject compositions,
the alcoholic components being cosmetically acceptable products,
in particular C.sub.1 -C.sub.4 lower alcohols, glycerol and alkyne
glycols.
The subject compositions can also contain other cosmetic or pharmaceutical
adjuvants and additives, in order to formulate topical compositions,
especially synthetic oils, thickeners, preservatives and basifying
or acidifying agents.
Even more effective lotions are formulated by combining the glucopyranoside
in synergistic compositions with other compounds which are already
known to impove hair growth or to retard hair loss, in particular:
(a) Minoxidil.RTM. or similar pyrimidine derivatives described
in U.S. Pat. No. 4,139,619; or
(b) Aminexil.RTM. or similar pyrimidine oxide derivatives described
in WO-96/09048, but also;
(c) retinoids such as trans-retinoic acid, isotretinoin, retinol
or vitamin A and derivatives thereof, such as the acetate, palmitate
or propionate, motretinide, etretinate and zinc trans-retinoate;
(d) antibacterial agents, especially erythromycin;
(e) calcium antagonists such as Cinnarizine and Diltrazem;
(f) hormones such as estriol or analogs thereof, or thyroxin or
salts thereof;
(g) antiandrogen agents such as oxendolone or spironolactone;
(h) 5-.alpha.-reductase inhibitors;
(i) OH radical scavengers;
(j) dyphylline and salts thereof;
(k) nicotinic acid esters, especially tocopheryl nicotinate, benzyl
nicotinate and C.sub.1 -C.sub.8 alkyl nicotinates such as methyl
or hexyl nicotinate;
(l) steroidal and non-steroidal anti-inflammatory agents, in particular
hydrocortisone and the salts and derivatives thereof, niflumic acid
and the like;
(m) citric acid esters, for example tributyl citrate.
Other compounds too can be added, namely, for example, salts, in
particular sodium, magnesium, calcium, zinc or copper salts, of
aliphatic acids or mixtures thereof, in particular of propionic
acid, butyric acid, valeric acid or undecylenic acid, aliphatic
acid esters, such as the methyl, ethyl and isopropyl esters, for
example undecylenic acid, hydroxycarboxylic or ketocarboxylic acids
and esters thereof, salicylic acid and derivatives thereof described
in FR-2,581,542, for example salicylic derivatives bearing an alkanoyl
radical having from 2 to 12 carbon atoms, cinnamic acid and derivatives
thereof, such as, for example, p-.beta.-D-glucopyranosyloxycinnamic
acid, substituted cinnamaldehydes such as, for example, p-methoxycinnamaldehyde,
ferulic acid, urea, terpenic alcohols such as, for example, thymol,
polymers such as, for example, starch, chitosan, chitin, hyaluronic
acid, alginates, proteins such as, for example, cereal globular
proteins, and the more or less advanced hydrolysis products of these
polymers, their complexes with copper, polyamino acids such as,
for example, polyglutamates, glycerol esters or polyglycerol esters,
in particular mono-, di- or oligoglyceryl fatty acid mono- or diesters,
for example mono- or oligoglyceryl cocoates, laurates or undecylenates,
polyalcohol ethers especially the glycerol, polyglycerol or pentaerythritol
ethers, saccharide monomers, dimers or oligomers such as, for example,
glucose, fructose, galactose or trehalose, saccharide esters such
as, for example, undecenyl trehalose described in JP-08,053,326,
the O-acyl glucose derivatives described in WO-93/02657, glycosides,
in particular ergosterol, stigmasterol or stigmastanol glycosides,
the alkyl polyglucosides also described in WO 93/02657, lactam forms
of saccharides such as, for example, L-arabino-1,5-lactam or D-glucurono-6,3-lactam
described in EP-0,334,586, lactones such as D (L) pantolactone,
.alpha.-pyrones such as those described in EP-0,672,406, such as,
for example, 5-methyl-.delta.-valerolactone, or lactone forms of
saccharides, in particular those described in EP-531,111, such as,
for example, D-fucono-1,5-lactone, compounds of alkanamido ammonium
type such as, for example, an alkanamidotrimethylpropylammonium,
a carboxymethylalkanamidodimethylpropylammonium, in particular derived
from lauric acid or undecylenic acid or from lauric/myristic fractions,
or (3-(docosanamido) propyl)trimethylammonium iodide or (3-(11-(dodecylthio)
undecanamido)propyl)-N,N,N-trimethylammonium iodide.
It has also been determined that these compounds influence the
bleaching of the hair.
The medium comprising these compositions generally includes glycerol,
matrix inherent to its preparation process excluding final purification,
water or mixtures of water and of a solvent or mixtures of solvents.
In order to further illustrate the present invention and advantages
thereof, the following specific examples are given, it being understood
that same are intended only as illustrative and in nowise limitative.
In said examples to follow, the individuals subjected to the experimentation
were male volunteers exhibiting accelerated alopecia and the beginning
of thinning of the hair and who had not been subjected to any hair
treatment for several months.
EXAMPLE 1
A lotion having the following composition was formulated:
(i) 2,3-dihydroxypropyl 2-(1-oxo-10-undecenyl) amino-2-deoxyglucopyranoside
5.0 g
(ii) glycerol 20.0 g
(iii) ethanol qs 100.0 g
(iv) fragrance qs
2 ml of this solution was topically applied to a wet head of hair
and to the scalp in the areas afflicted with alopecia, at a frequency
of twice per day. A marked slowing of hair loss (noted on brushing)
was observed from the 12th week of application and regrowth of hair
on the frontal lobes was observed in more than 30% of the individuals
from the 6.sup.th month.
Comment: the 100 g of ethanol can, without any disadvantage, be
replaced by a 20/80 propylene glycol/isopropanol mixture.
EXAMPLE 2
The following composition was formulated:
(i) 2,3-dihydroxypropyl 2-(1-oxo-10-undecenyl) amino-2-deoxyglucopyranoside
10.0 g
(ii) glycerol 40.0 g
(iii) Oramix.RTM.NS1 10.0 g
(iv) Natrosol.RTM. 0.5 g
(v) fragrance qs
(vi) water qs 100.0 g
In this formulation, Oramix.RTM.NS10 (SEPPIC) is an alkylpolyglucoside
containing three glucose units (hydrophilic portion) and C10/C12/C14
chains (lipophilic portion), in a composition containing 55% active
material, with a foaming agent function; Natrosol.RTM. is a cetyl-
or 2-hexadecyl hydroxyethylcellulose thickener marketed by Aqualon.
Results similar to those described in Example 1 were observed;
however, the formula allows more uniform distribution of the product,
by means of better foaming.
EXAMPLE 3
The following composition was formulated:
(i) glycerol 40.0 g
(ii) Oramix.RTM.NS1 10.0 g
(iii) Natrosol.RTM. 0.5
(iv) fragrance qs
(v) water qs 100.0 g
No effect was observed, either on regrowth of the hair or on reducing
hair loss, even after six months of daily application of 2 ml of
the solution onto wet hair and onto the areas afflicted with alopecia.
EXAMPLE 4
The following composition was formulated:
(i) 2,3-dihydroxypropyl 2-(1-oxo-10-undecenyl) amino-2-deoxyglucopyranoside
3.0 g
(ii) glycerol 15.0 g
(iii) sodium cocoamphodiacetate containing 38% active material
5.0 g
(iv) alginic acid 0.5 g
(v) fragrance qs
(vi) water qs 100.0 g
The sodium cocoamphodiacetate was Miranol.RTM.C2M Rhone-Poulenc;
the alginic acid was Texamid.RTM.778 marketed by Henkel.
Results similar to those described in Example 1 were observed with
this formula. The ease of uniform application was the same as for
that of Example 2.
EXAMPLE 5
Mixed composition:
The lotion having the following composition was formulated:
(i) 2,3-dihydroxypropyl 2-(1-oxo-10-undecenyl) amino-2-deoxyglucopyranoside
5.0 g
(ii) glycerol 20.0 g
(iii) Minoxidil.RTM. 5.0 g
(iv) ethanol qs 100.0 g
(v) fragrance qs
2 ml of this solution were topically applied to wet hair and to
the areas afflicted with alopecia, at a frequency of two applications
per day. The results observed, both in terms of the slowing of hair
loss and the regrowth of hair on the frontal lobes, were from about
10% to 20% greater than those observed in Examples 1 and 2.
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. |