Hair loss abstract
Dermatological/cosmetic compositions for reducing or decelerating
human hair loss comprise an effective hair loss-reducing amount
of combinatory immixture of (a) at least one antifungal agent and
(b) at least one halogenated antibacterial agent other than a macrolide
or pyranoside, characteristically formulated in a topically physiologically
acceptable medium therefor.
Hair loss claims
What is claimed is:
1. A method for reducing or decelerating hair loss from a human
subject in need of such treatment, comprising topically applying
a dermatological/cosmetic composition of matter comprising an effective
hair loss-reducing amount of a combinatory immixture of (a) at least
one antifungal agent and (b) at least one halogenated antibacterial
agent other than a macrolide or pyranoside wherein said at least
one antifungal agent is selected from the group consisting of 6-
cyclohexyl-l-hydroxy-4-methyl-2(1H)-pyridone, 1-hydroxy-4-methyl-6-
(2,4,4trimethylpentyl)-2-(1H)-pyridone and 1-(4-chlorophenoxy)-l-(1H-imidazolyl)-
3,3-dimethyl-2-butanone and said at least one halogenated anti-bacterial
agent is selected from the group consisting of 5-chloro-2-(2,4dichlorophenoxy)phenol,
chlorhexidine and chloramphenicol wherein from 0.01% to 5 5 by weight
of said at least one antifungal agent and 0.01% to 10% by weight
of said at least one halogenated antibacterial agent is contained
in said composition.
2. The method as defined by claim 1, wherein from 0.1% to 2% by
weight of said at least one antifungal agent (a) is contained in
said composition.
3. The method as defined by claim 1, wherein from 0.1% to 2% by
weight of said at least one halogenated antibacterial agent (b)
is contained in said composition.
4. The method as defined by claim 1, wherein the weight ratio of
said at least one antifungal agent contained in said topically administered
composition (a) to said at least one halogenated antibacterial agent
(b) ranges from 0.2 to 10.
5. The method as defined by claim 1, wherein said topically administered
composition is formulated into a topically physiologically acceptable
medium therefor.
6. The method as defined by claim 5, wherein said topically administered
composition is selected from the group consisting of a lotion, shampoo,
foam, cream, gel, ointment, salve, milk, stick, spray, balm, emulsion,
powder, solid soap or liquid soap.
7. The method as defined by claim 6, said topically administered
composition further comprising at least one topically pharmaceutically
acceptable additive or adjuvant.
8. The method as defined by claim 7, wherein said at least one
additive or adjuvant is selected from the group consisting of a
thickening agent, preservative, stabilizer, pH regulator, osmotic
pressure modifier, emulsifying agent, sunscreen agent, antioxidant,
fragrance, colorant, polymer, surface-active agent and mixture thereof.
Hair loss description
BACKGROUND OF THE INVENTION
1. Technical Field of the Invention
The present invention relates to novel dermatological/cosmetic
compositions comprising at least one antifungal agent and at least
one halogenated antibacterial agent, other than those of the genera
macrolide and pyranoside, and to topical applications thereof for
the reduction of hair loss.
2. Description of the Prior Art
It has long been known to this art that natural hair loss in humans
reflects the overall equilibrium of hair follicles between the alternating
growth phases (anagenic phases) and the hair loss phases (telogenic
phases). The average ratio of the number of follicles in the anagenic
phase to that in the telogenic phase is on the order of 9 (90/10).
The percentage of follicles in the rest or quiescent phase (catagenic
phase) appears to be very low.
Natural hair loss may be estimated, on average, to be a few hundred
hairs per day for a normal physiological state. For a pathological
physiological state, this number may attain a value of several hundred
per day, leading to alopecia.
Moreover, a microbiological flora exists at the surface of the
scalp, this flora consisting naturally of bacteria and yeasts. When
an imbalance occurs in the natural composition of this flora, hair
loss may be increased.
It too is known, moreover, that certain factors such as hormonal
imbalance, physiological stress or food deficiencies may accelerate
the phenomenon.
In order to reduce hair loss, FR-2,618,068 describes treatment
of the scalp with a composition containing an antifungal agent which
is optionally combined with an anti-inflammatory agent and/or with
an antibiotic agent selected from among the macrolides or the pyranosides.
However, such compositions are not entirely satisfactory since,
although the reduction of hair loss is more pronounced than with
treatment using an antifungal agent alone, topical application of
anti-inflammatory agents have a tendency to bring about variations
in the natural composition of the microbiological flora, thereby
increasing the risks of infection.
Antibiotic agents are not entirely satisfactory either, since they
are often unstable in cosmetic or dermatological compositions. In
addition, they promote bacterial resistance phenomena, thus resulting
in lesser effectiveness of the compositions intended to reduce or
decelerate hair loss.
The topical application of antibacterial agents does not promote
these resistance phenomena, but it appears that most of the conventional
antibacterial agents inhibit the action of antifungal agents, thereby
also reducing the effectiveness of compositions containing this
type of combination.
SUMMARY OF THE INVENTION
It has now unexpectedly been determined that compositions intended
to reduce or decelerate hair loss and containing an antifungal agent
are more effective when this agent is combined with a halogenated
antibacterial agent not of the macrolide and pyranoside families;
surprisingly, these halogenated antibacterial agents do not inhibit
the action of antifungal agents as is the case with the nonhalogenated
antibacterial agents.
In addition, such halogenated antibacterial agents are very stable
when they are formulated into the compositions of the invention
and they promote no bacterial resistance.
Briefly, the present invention thus features novel dermatological/cosmetic
compositions comprising at least one antifungal agent and at least
one halogenated antibacterial agent, other than those of the genera
macrolide and pyranoside, and to topical applications thereof for
the reduction of hair loss.
DETAILED DESCRIPTION OF BEST MODE AND PREFERRED EMBODIMENTS OF
THE INVENTION
More particularly according to the present invention, it is observed
that after a few weeks of treatment, the appearance of the hair
is improved, and the hair is, in particular, shinier, lighter and
less greasy.
According to the invention, by the term "antifungal agent"
is intended any substance capable of inhibiting or preventing the
growth of yeasts, in particular those found at the surface of the
epidermis which is rich in sebaceous glands and especially at the
surface of the scalp such as, for example, Pityrosporum ovale and
varieties thereof (Pityrosporum orbiculare and Malassezia furfur).
Among the antifungal agents suitable for formulation according
to the invention, particularly representative are terbinafine, zinc
pyrithione, selenium sulfide, tars and derivatives thereof, undecylenic
acid and salts thereof and hydroxypyridone derivatives such as CICLOPIROX,
i.e., 6-cyclohexyl-1- hydroxy-4-methyl-2-(1H)-pyridone, or OCTOPIROX,
i.e., 1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)- 2-(1H)-pyridone.
These antifungal agents are preferably present in the compositions
in accordance with this invention at a concentration ranging from
0.01% to 5% by weight approximately relative to the total weight
of the composition. Even more preferably, the concentration of antifungal
agents may range from 0.1% to 2% by weight relative to the total
weight of the composition.
Also according to the invention, by the term "halogenated
antibacterial agent" is intended any substance containing at
least one halogen atom and capable of inhibiting or preventing the
growth of the bacterial flora present at the surface of epidermis
which is rich in sebaceous glands.
The halogenated antibacterial agents according to the present invention
are preferably benzene derivatives.
Among the halogenated antibacterial agents suitable for formulation
according to the invention, particularly exemplary are chlorinated
antibacterial agents such as triclosan, i.e., 5-chloro-2-(2,4- dichlorophenoxy)phenol,
marketed under the trademark IRGASAN by Ciba-Geigy, chlorhexidine
and derivatives thereof, chloramphenicol and 1-(4-chlorophenoxy)-1-(1H-
imidazolyl)-3,3-dimethyl-2-butanone, marketed under the trademark
CLIMBAZOLE by Bayer. These halogenated antibacterial agents are
preferably present in the compositions in accordance with the invention
at a concentration which may range from 0.01% to 10% by weight approximately
relative to the total weight of the composition. Even more preferably,
the concentration of antibacterial agents may range from 0.1% to
2% by weight relative to the total weight of the composition.
The weight ratio of the antifungal agents to the halogenated antibacterial
agents may vary over wide limits. In particular, this weight ratio
preferably ranges from 0.2 to 10.
The compositions in accordance with this invention may be in various
forms typically employed in cosmetics or in dermatology for the
treatment of the scalp.
They may, more particularly, be formulated with a topically physiologically
(dermatologically/cosmetically) acceptable vehicle, carrier or diluent
in the form of lotions, shampoos, foams, creams, gels, sticks, sprays,
balms, ointments, milks, salves, emulsions, powders, or solid or
liquid soaps.
The physiologically acceptable medium generally comprises water
or of a mixture of water and at least one organic solvent which
is physiologically acceptable for the purpose of a topical application.
Among these solvents, exemplary are acetone, C.sub.1 -C.sub.4 lower
alcohols such as ethanol and isopropyl alcohol, alkylene glycols
such as ethylene glycol and propylene glycol, ethylene glycol monomethyl,
monoethyl or monobutyl ethers, the monoethyl ethers of propylene
glycol and of dipropylene glycol, the C.sub.1 -C.sub.4 alkyl esters
of short-chain acids and polytetrahydrofuran ethers. When these
are indeed present, such solvents preferably constitute from 1%
to 80% by weight of the total weight of the composition.
The medium may be thickened using thickening agents typically employed
in cosmetics or in pharmaceuticals.
Among these thickening agents, particularly exemplary are cellulose
and derivatives thereof such as cellulose ethers, heterobiopolysaccharides
such as xanthan gum, scleroglucans, and polyacrylic acids which
either may or may not be crosslinked.
The thickening agents are preferably present in proportions ranging
from 0.1% to 5% by weight approximately relative to the total weight
of the composition.
Depending on the intended application of the subject compositions,
one skilled in this art can easily select the particular compounds
and adjuvants that are necessary and characteristically employed
to formulate these compositions.
Among these adjuvants or additives, especially representative are
preservatives, stabilizing agents, pH regulators, osmotic pressure
modifiers, emulsifying agents, sunscreen agents, antioxidants, fragrances,
colorants, anionic, cationic, nonionic, amphoteric or zwitterionic
surface-active agents or mixtures thereof, polymers, and the like.
In addition to the particular antifungal/antibacterial species
according to the invention, the subject compositions may also contain
compounds already known for reducing or decelerating hair loss.
This invention also features a cosmetic treatment for the hair
and/or the scalp, comprising applying thereto a composition as described
above, for the purpose of reducing hair loss.
The preferred regime or regimen of application comprises applying
1 to 20 g of the composition to all or to certain parts of the scalp,
at a frequency of one to two applications per day, for 1 to 7 days
per week, for a period of time of from 1 to 6 months or even longer.
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
A shampoo having the following composition was formulated:
______________________________________ (a) Sodium lauryl ether
sulfate 12 g containing 2.2 mol of ethylene oxide (b) Coconut monoisopropanolamide
3.5 g (c) Hydroxypropylcellulose quaternized 0.4 g with triethanolamine
(d) 1-Hydroxy-4-methyl-6-(2,4,4- 0.3 g trimethylpentyl)-2-(1H)-pyridone,
marketed under the trademark OCTOPIROX by Hoechst (e) Triclosan
marketed under the 0.25 g trademark IRGASAN by Ciba-Geigy (f) Preservative
0.3 g (g) Fragrance 0.4 g (h) Water qs 100 g ______________________________________
When used regularly 2 to 3 times per week, this shampoo reduced
hair loss, while at the same time improved the general appearance
of the hair.
EXAMPLE 2:
A lotion for the scalp having the following composition was formulated:
______________________________________ (a) Ethyl alcohol 38 g (b)
Castor oil 0.2 g (c) Chorhexidine gluconate marketed 0.4 g by ICI
(d) Undecylenic acid 0.25 g (e) Fragrance 0.3 g (f) Dye 0.05 g (g)
Water qs 100 g ______________________________________
When applied daily to the scalp and the hair, without rinsing,
this lotion reduced hair loss, while at the same time improved the
general appearance of the hair.
EXAMPLE 3
A foam for the scalp having the following composition was formulated:
______________________________________ (a) Diallyldimethyl ammonium
chloride 1.5 g polymer marketed under the trademark MERQUAT 100
by Merck (b) Hydroxyethylcellulose and 0.3 g diallyldimethyl ammonium
chloride copolymer marketed under the trademark CELQUAT LOR by National
Starch (c) Quaternary ammonium salt 0.3 g marketed under the trademark
ARQUAD 16-25W by AKZO (d) Silicon gum marketed under the 0.1 g trademark
QC F2-1671 by Dow Corning (e) Propylene glycol 5 g (f) Phenoxyethanol
0.4 g (g) 1-Hydroxy-4-methyl-6-(2,4,4- 0.2 g trimethylpentyl)-2-(1H)-pyridone,
marketed under the trademark OCTOPIROX by Hoechst (h) Chloramphenicol
0.3 g (i) Water qs 100 g ______________________________________
After regular application of this foam, a reduction in hair loss
and an improvement in the general appearance of the hair were observed.
EXAMPLE 4
A spray for the scalp having the following composition was formulated:
______________________________________ (a) Isoparaffin hydrocarbon
(isobutane 0.5 g marketed by Huls) (b) Polydimethylsiloxane marketed
under 1.2 g the trademark DC 200 FLUID by Dow Corning (c) Polyaminosiloxane
marketed under 0.4 g the trademark DC 929 EMULSION by Dow Corning
(d) Ethanol 15 g (e) Crosslinked acrylic acid polymer 0.1 g marketed
under the trademark CARBOPOL 980 by Goodrich (f) Triclosan marketed
under the 0.35 g trademark IRGASAN by Ciba-Geigy (g) 1-Hydroxy-4-methyl-6-(2,4,4-
0.1 g trimethylpentyl)-2-(1H)-pyridone, marketed under the trademark
OCTOPIROX by Hoechst (h) Undecylenic acid 0.15 g (i) Triethanolamine
qs pH 7 (j) Water qs 100 g ______________________________________
This composition was packaged in a pump-dispenser bottle.
After regular application of this spray, a reduction in hair loss
and an improvement in the general appearance of the hair were observed.
EXAMPLE 5:
A lotion for combating hair loss having the following composition
was formulated
______________________________________ (a) 1-(4-Chlorophenoxy)-1-(1H-
0.1 g imidazolyl)-3,3-dimethyl-2-butanone, marketed under the trademark
CLIMBAZOLE by Bayer (b) Undecylenic acid 0.15 g (c) Ethanol 38 g
(d) Fragrance qs (e) Dye qs (f) Water qs 100 g ______________________________________
When applied daily to the hair, without rinsing, this lotion reduced
hair loss, while at the same time improved the general appearance
of the hair.
EXAMPLE 6
Tests of effectiveness:
The following lotion was formulated in order to demonstrate the
effectiveness of the compositions of the invention:
______________________________________ (a) 1-Hydroxy-4-methyl-6-(2,4,4-
0.25 g trimethylpentyl)-2-(1H)-pyridone, marketed under the trademark
OCTOPIROX by Hoechst (b) Triclosan marketed under the 0.3 g trademark
IRGASAN by Ciba-Geigy (c) Ethanol 45 g (d) Fragrance qs (e) Water
qs 100 g ______________________________________
This lotion was supplied to 20 male individuals displaying androgenic
alopecia. They applied this composition to the scalp, without rinsing,
once a day for 9 months. During the course of this study, a standardized
questionnaire was periodically given to each individual.
The results obtained are reported in the tables below.
(A) Appearance of the hair:
These individuals described themselves in respect of the greasy,
lackluster, sticky or normal nature of their hair.
The results collected are reported in Table I below:
TABLE I ______________________________________ Time in Months 0
0.5 1 1.5 2 3 4 5 6 7 8 9 ______________________________________
Greasy hair 19 5 3 4 2 3 1 3 2 2 2 3 Non-greasy 1 15 17 16 18 17
19 17 18 18 18 17 6 hair Lacklustre 7 6 6 3 2 1 1 1 1 1 2 1 hair
Non-lacklustre 13 14 14 17 18 19 19 19 19 19 18 19 hair Sticky hair
17 2 1 0 0 0 0 0 0 0 0 0 Non-sticky hair 3 18 19 20 20 20 20 20
20 20 20 20 Normal hair 1 13 16 16 18 17 16 16 17 17 18 1 8 Abnormal
hair 19 7 4 4 2 3 4 4 3 3 2 2 ______________________________________
It was observed that the very large majority of the individuals
observed a general normalization in the state of their hair from
the first weeks of treatment, especially as regards the greasy,
lacklustre and sticky appearance thereof.
(B) Change in the seborrhoea:
These individuals evaluated the variations in their seborrhoea,
which could be increased, stable or reduced. The results obtained
are reported in Table II below:
TABLE II ______________________________________ Time in Months
0.5 1 1.5 2 3 4 5 6 7 8 9 ______________________________________
Increased 3 1 0 0 0 0 1 0 0 1 0 seborrhoea Stable seborrhoea 15
11 14 15 14 14 12 13 12 11 10 Reduced seborrhoea 2 8 6 5 6 6 7 7
6 8 10 ______________________________________
It was observed that after a transitory phase of increased seborrhoea
in a minority of individuals, a normalization of the seborrhoea
was established. No reactional seborrhoea was detected.
(C) Observation of pruritus:
These individuals reported the presence or absence of pruritus.
The results obtained are reported in Table III below:
TABLE III ______________________________________ Time in Months
0 0.5 1 1.5 2 3 4 5 6 7 8 9 ______________________________________
Pruritus 16 12 0 0 0 0 1 0 1 0 1 0 Absence of 4 8 20 20 20 20 19
20 19 20 19 20 pruritus ______________________________________
It was observed that a very marked improvement was established
from the first weeks of treatment.
(D) Observation of hair loss:
Hair loss was estimated by these individuals. At each consultation,
envelopes containing hairs of a similar color to their own and of
different amounts ranging from about 10 to about 150 were given
to them. Each individual then indicated the envelope which corresponded
best to the estimation of their hair loss during shampooing.
The results are given according to whether the hair loss increased,
remained stable or was reduced over the course of the application/treatment.
These results obtained are reported in Table IV below:
TABLE IV ______________________________________ Time in Months
0.5 1 1.5 2 3 4 5 6 7 8 9 ______________________________________
Increased hair loss 9 3 1 0 0 0 0 0 0 0 0 Stable hair loss 8 13
12 13 12 10 6 7 7 7 8 Reduced hair loss 3 4 7 7 8 10 14 13 13 13
12 ______________________________________
For the majority of the individuals, a significant reduction in
hair loss was observed after application of the composition for
a few weeks. This reduction tended to stabilize after application
for 5 to 6 months.
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. |