Hair loss abstract
Formulations for the prevention and therapy of hair loss and seborrhoea
are based on essential oils obtainable through alcoholic distillation
of plants which contain the essential oils, combined with salicylic
acid and with fatty acids having 10 to 40 carbon atoms.
Hair loss claims
What is claimed is:
1. Hydroalcoholic mixture of beta-pinene, camphene, beta-myrcene,
limonene, cineole (1,8-epoxy-p -methane), camphor, linalol, bornyl
acetate, isobornyl acetate, menthol, terpinen-ol, isoborneol monoterpens,
having a chromatogram as shown in the Figure.
2. Combination of the mixture of claim 1 with salicylic acid or
the salts thereof and with C.sub.10 -C.sub.14 saturated or unsaturated
fatty acids.
3. Combination according to claim 2, wherein the mixture is present
in a concentration comprised between 5 and 20% w/w, the salicylic
acid between 0.1 and 1%, the fatty acids between 0.1 and 0.5%.
4. Combination according to claim 3, wherein said mixture is present
in a concentration of 10%, the salicylic acid in a concentration
of 0.3%, the fatty acids in a concentration of 0.25%.
5. Cosmetic formulations containing the combination of claim 2
in admixture with carriers and excipients pharmaceutically acceptable.
6. Formulations according to claim 5 in the form of hydroalcoholic
lotions and gels.
7. Process for the preparation of the mixture of claim 1, which
comprises the steps of:
a) steeping in 70% ethanol one or more parts selected from the
group consisting of roots, rhizomes, leaves, bark and seeds from
Curcuma zedoaria, Myristica fragrans, Cinnamonum cassia, Eugenia
aromatics, Acorus calamus, Zingiber officinalis, Alpinia officinarum,
Ferula galbaniflua, Liquidambar orientalis, Aloe vera, Cannarium
commune, Commiphora molmol, Arnica montana, Rosmarinus officinalis,
together with terpentine oil, for two days with stirring at room
temperature;
b) distilling the product of step a) at 40.degree. C. at room pressure;
and
c) diluting the distillate of step b) with water and removing the
insoluble oleous residue.
8. Process according to claim 7 wherein the plants or the parts
thereof are used in amounts comprised between 10 and 50 g for each
plant.
9. Process according to claim 8, wherein the amount is 20 g.
10. Hydroalcoholic mixture obtainable by the process of claim 7.
11. A method for the treatment of hair loss and of seborrhoea comprising
applying to a human scalp a cosmetic formulation prepared from the
hydroalcoholic mixture of claim 1, as such or in combination with
salicylic acid or the salts thereof and with C.sub.10 -C.sub.14
saturated or unsaturated fatty acids.
12. Cosmetic formulations containing the combination of claim 3
in admixture with carriers and excipients pharmaceutically acceptable.
13. Cosmetic formulations containing the combination of claim 4
in admixture with carriers and excipients pharmaceutically acceptable.
14. Formulations according to claim 12, in the form of hydroalcoholic
lotions and gels.
15. Formulations according to claim 13, in the form of hydroalcoholic
lotions and gels.
Hair loss description
The present invention provides new formulations useful in the prevention
and therapy of hair loss, based on the combination of substances
with vasokinetic, antibacterial and antiandrogenic activities. It
is known from the literature and from the cosmetic practice that
the hair loss is negatively influenced by a reduced periferic microcirculation
in the "galea capitis", by its altered relation with the
bacterial flora and by an altered local androgenic methabolism.
The androgens, in particular the increased deposit of dihydrotestosterone
in the hair bulb, are considered to play an important role in the
pathogenesis of androgenic alopecia.
In Japanese patent JP-8310923, the essential oils obtained by steam
distillation of Citrus aurantium peels, and of Salvia officinalis,
Mentha piperita, Eucaliptus globulus, Artemisia princeps and Rosmarinus
officinalis leaves and flowers, are considered inhibitors of testosterone
5-alpha-reductase and therefore useful in the treatment of alopecia,
hirsutism and seborrhoea. European patent EP-433131A claims essential
oils incorporated in lipidic material in the presence of known vasodilators
like methyl nicotinate or other synthetic compounds for the prevention
of hair loss or of dandruff formation, and like antiparasites. The
chemical composition of these essential oils is not reported and
their effects are likely mediated by other synthetic compounds present
in the final formulations.
Now, a mixture of monoterpenes obtained through alcoholic extraction
followed by distillation of some plants alone or in combination,
has surprisingly shown vasokinetic, antibacterial and antiseborrhoic
activities. The antibacterial activity which was known for the essential
oils, was never associated to a marked vasokinetic activity, which
was demonstrated by the control of the blood flow in cutaneous areas
treated before and after the application of the mixture, using Laser
Doppler technique and computer videocapillary-scopy.
The monoterpene mixture, combined with salicylic acid which is
known to strongly inhibit cyclooxygenase I and II, and with saturated
and unsaturated fatty acids having acyl chains from 10 to 14 carbon
atoms, in particular 12 carbon atoms like lauric and myristic acids,
has shown particularly useful for the treatment of hair loss in
normal conditions and in androgenic alopecia. The monoterpene mixture
can be obtained by mixing the single commercial monoterpenes in
suitable ratios, or better by mixing roots, rhizomes, leaves, barks
and seeds of some hexotic plants containing essential oils, which
so far have never been used in cosmetics for the prevention or the
therapy of hair loss (with the exception of rosemary oil, the cosmetic
use of which is known and it is based on mechanisms different from
those reported in the present invention), by steeping the same in
70% ethanol and finally by collecting the alcohol which contains
the desired monoterpens through distillation at room pressure.
For example, the mixture of essential oils can be obtained by steeping
in 70% aqueous ethanol similar amounts of rhizomes from Curcuma
longa, Myristica fragrans, Ferule galbaniflua, Liquidambar orientalis,
Alpinia officinarum, Acorus calamus, Aloe vera, Cannarium commune,
Commiphora molmol, Eugenia aromatica, Cinnamonum cassia, Curcuma
zedoaria, Arnica montana, Rosmarinus officinalis and lower amounts
of oil of turpentine, the vegetal material amount being comprised
between 10 and 50 g, preferably 20 g of each plant, in 1.2 1 of
70% ethanol for two days with stirring at room temperature, then
distilling the alcohol at room pressure and collecting from 0.7
to 0.95 1 of distillate, preferably 0.850 lt; this distillate, after
suitable water dilution, preferably up to 50% w/w, can be used as
such, after removal of the insoluble oily residue, to inhibit hair
loss or it can serve as the basis for the addition of other active
ingredients. In particular the mixture obtained through distillation,
combined with salicylic acid and menthol, after dilutions with 25
to 75% w/w hydroalcoholic solutions, preferably up to 50%, is steeped
for a period of 3 to 60 days, preferably 30 days, and it is used
after removal of insoluble oily residues.
Said hydroalcoholic mixture, which contains as the main ingredients
beta-pinene, camphene, beta-myrcene, limonene, cineole (I,8-epoxy-p-menthane),
camphor, linalool, bornyl acetate, isobornyl acetate, menthol, terpinen-ol,
isoborneol, in ratios corresponding to the gas chromatogram of the
Figure, is the first object of the invention. Said chromatogram
was obtained using a HP-Innowax column (cross -linked polyethylene
glycol, N. of part 19091 N-133, 30 m.times.0.25 mm I.D., 0.25 .mu.m
film thickness), according to the following temperature program:
60.degree. C..times.5 min, 60.degree. C. to 250.degree. C. at 3.degree./min,
250.degree. C. for 3 min; injection with PTV (Programmed Temperature
Vaporizer), from 120.degree. C. to 250.degree. C. The addition to
the mixture of salicylic acid or the salts thereof and of fatty
acids with anti androgenic activity, results in a surprising synergistic
effect which reduces the hair loss improving the hair growth and
strength. Therefore, a second object of the invention is represented
by a formulation which contains the above described mixture in combination
with salicylic acid or the salts thereof, and with saturated or
unsaturated C.sub.10 -C.sub.14 fatty acids.
According to a preferred embodiment of the invention, the mixture
of essential oils is obtained by steeping 20 g of Curcuma zedoaria
rhizomes, 20 g of Myristica fragrans seeds, 20 g of Cinnamomum cassia
branch bark, 20 g of Eugenia aromatica flowers, 20 g of Acorus calamus
rhizomes, 20 g of Zingiber officinalis rhizomes and 20 g of Alpinia
officinarum, in 0.9 1 ethanol. After one day, resin oils of Ferula
galbaniflua, Liquidambar orientalis, Aloe vera, Cannarium commune,
Commiphora molmol, Arnica Montana, Rosmarinus officinalis and turpentine
oil are added to the steeped product in amounts variable from 5
to 50 g, to favour the alcohol dispersion of the resin oils.
Afterwards water is added up to an alcoholic grade of about 70%
and after stirring the mixture for two hours at 40.degree. C., the
distillation is started and about 0.85 1 of alcoholic distillate
are collected. The distillate is a colourless clear liquid with
a strongly aromatic smell.
The distillate, without the addition of other substances, has vasokinetic,
antibacterial and antiseborrhoic activities.
The monoterpene-containing hydroalcoholic mixture increases the
volume and flow-rate at the capillary level, which, as mentioned
above, is extremely important in the primitive and secondary alopecia.
In fact, when the mixture is applied on the cutis, it integrates
the blood flow in various organic districts and in particular it
increases the blood flow in the "galea capitis" as it
results from the data reported in table I, wherein the flow increment
has been tested using Laser Doppler.
TABLE I Cutaneous blood flow variations determined using Laser
Doppler after single administration of the alcoholic distillate
1:1 diluted with water. Substances 0 30' 60' 90' 120' Distillate
4.45 13.33 14.12 9.7 10.32 Placebo 5.24 5.63 7.78 4.64 6.61
The administration of the formulations of the invention for periods
variable from one week to three months causes in humans a remarkable
reduction of androgenic alopecia as it results from the data reported
in tables II and III. Table II reports the flow increase caused
by the application of the formulation of the example I, as evidenced
by Laser Doppler analysis. Laser Doppler flowmetry was performed
to test the vasokinetic effects, using the PeriFlux(R) PF3 flowmeter
which is an instrument emitting a subtle bundle of 632 nm wavelenght
monocromatic light, which is produced by a low potency He--Ne laser
source. By this technique, the scalp blood flow was measured in
basal conditions and after the application of the test products,
with an interval of 15 min from the first application (acute effect)
and after 30, 60 and 90 day treatment (chronic effect). The results
are reported in table II.
TABLE II Mean blood capillary flow effects induced by the topical
application (90 days) of the lotion prepared according to the example
I. Capillary flow (AU30 m .+-. e.s.) Treatment Basal 15 min 30 days
60 days 90 days Alcoholic distillate 9.2 .+-. 1.0 23.1 .+-. 3.0*
11.7 .+-. 2.4 16.8 .+-. 1.2* 16.7 .+-. 1.1* Placebo 9.4 .+-. 1.2
10.0 .+-. 1.3 10.7 .+-. 1.5 11.0 .+-. 1.1 11.5 .+-. 0.9 Comp. lotion
9.3 .+-. 1.1 24.0 .+-. 3.1* 18.1 .+-. 2.5 20.1 .+-. 1.3* 19.4 .+-.
1.0* *= p < 0.01 vs basal as the result of the variance analysis
of a split-plot graphic (Bonferroni's t). N = 10.
The trichograms of tested subjects randomly divided into 10 groups,
were performed in order to evaluate the effect of the formulations
on the hair loss inhibition at the beginning and at the end (90
days) of the treatment. The trichogram consists in the withdrawal
of a suitable number (about 50) of hairs using rubberized forceps,
from the superior-frontal and latero-nuchal areas.
The microscopic examination of hair roots allows to evaluate the
hair quantity which is in the anagen (growth), catagen (mature)
and telogen (rest) phase. The reduction in the anagen percentage
and the increase in the telogen percentage, with respect to normal
values (which are about 85-90% and 10-15%, respectively), represent
the clinical evidence of a pathological hair loss.
TABLE III Trichogrammic effects induced by the topical application
(90 days) of the lotion prepared according to the example I Trichogram
(% - m .+-. e.s.) Treatment telogen anagen + catagen Alc. dist.
Before 76 .+-. 3 24 .+-. 1 After 90 days 81 .+-. 3 19 .+-. 1 Alc.
dist. + Before 78 .+-. 2 22 .+-. 1 Salic. Ac. After 90 days 82 .+-.
2 18 .+-. 1 Ac. + dist. Before 74 .+-. 2 26 .+-. 2 Ac. salic. +
After 90 days 86 .+-. 3* 14 .+-. 1* Fats *= p < 0.01 vs basal
as the result of the calculation.
As it comes out from the data reported above, the alcoholic distillate
topically applied for long periods, by the dayly administration
of the preparation, exerts time-persisting favourable microvasculokinetic
effects on the cutis. The trichological pharameters, telogen, anagen
and catogen, behave in a similar manner. The combination of the
distillate with other substances like the low molecular weight saturated
and unsaturated fatty acids, which interfere with androgen receptors,
leads to a clear improvement of the telogen-anagen-catagen ratios.
The skin treatment through an increased blood flow and the consequent
increase of nutritive substances, after few days results in a clear
cutaneous modification with the increase of the number of perfused
capillaries and with dandruff absence; the hair bulbs are normal
and patent, with a normal sebaceous production.
The cosmetic formulations of the invention are in the form of hydroalcoholic
lotions (which are preferred for the treatment of the scalp) or
in the form of gels, and are used in the treatment of hair loss
and seborrhoea.
The combinations which are preferred for the treatment comprise
the hydroalcoholic mixture in a concentration between 5 and 20%,
preferably 10%, the fatty acids between 0.1 and 0.5%, preferably
0.25%, and the salicylic acid between 0.1 and 1%, preferably 0.3%.
The treatment with these substances ranges from few days to six
months. Examples of formulations according to the invention are
hereafter illustrated but in any case they are not intended to limit
the invention.
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