U.S. patent application number 11/331011 was filed with the patent office on 2006-05-18 for use of metalloprotease inhibitors to induce and/or stimulate the growth of head hair or other hairs and/or to slow down their loss.
This patent application is currently assigned to L'OREAL. Invention is credited to Francoise Jarrousse, Yann Mahe.
Application Number | 20060105006 11/331011 |
Document ID | / |
Family ID | 9526261 |
Filed Date | 2006-05-18 |
United States Patent
Application |
20060105006 |
Kind Code |
A1 |
Jarrousse; Francoise ; et
al. |
May 18, 2006 |
Use of metalloprotease inhibitors to induce and/or stimulate the
growth of head hair or other hairs and/or to slow down their
loss
Abstract
A method for inducing and/or stimulating the growth of hair
and/or slowing down hair loss comprising administering an effective
amount of at least one metalloprotease inhibitor or any functional
biological equivalent thereof and an acceptable carrier
therefor.
Inventors: |
Jarrousse; Francoise;
(Livry-Gargan, FR) ; Mahe; Yann;
(Morsang-sur-Orge, FR) |
Correspondence
Address: |
BUCHANAN INGERSOLL PC;(INCLUDING BURNS, DOANE, SWECKER & MATHIS)
POST OFFICE BOX 1404
ALEXANDRIA
VA
22313-1404
US
|
Assignee: |
L'OREAL
Paris
FR
|
Family ID: |
9526261 |
Appl. No.: |
11/331011 |
Filed: |
January 13, 2006 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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10677284 |
Oct 3, 2003 |
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11331011 |
Jan 13, 2006 |
|
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09700195 |
Feb 20, 2001 |
6645477 |
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PCT/FR99/01124 |
May 11, 1999 |
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10677284 |
Oct 3, 2003 |
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Current U.S.
Class: |
424/401 ;
514/575 |
Current CPC
Class: |
A61K 8/14 20130101; A61Q
7/00 20130101; A61Q 5/00 20130101; A61K 8/64 20130101; A61K 31/19
20130101; A61K 2800/782 20130101 |
Class at
Publication: |
424/401 ;
514/575 |
International
Class: |
A61K 31/19 20060101
A61K031/19; A61K 8/42 20060101 A61K008/42 |
Foreign Application Data
Date |
Code |
Application Number |
May 12, 1998 |
FR |
98/05968 |
Claims
1. A method for inducing and/or stimulating the growth of hair
and/or slowing hair loss comprising applying to the hair and/or the
scalp of an individual in need thereof, a topical composition
comprising an effective amount of at least one metalloprotease
inhibitor other than chelating calcium ions and growth factors, in
a physiologically acceptable medium.
2. A method for inducing and/or stimulating the growth of hair
and/or slowing hair loss comprising applying to the hair and/or the
scalp of an individual in need thereof, a topical composition
comprising an effective amount of at least one metalloprotease
inhibitor selected from the group consisting of tissue inhibitors,
cytokines, oncogenic products, matrix inhibitors, and chemical
inhibitors other than chelating calcium ions, in a physiologically
acceptable medium.
3. A method according to claim 2, wherein the metalloprotease
inhibitor is a chemical inhibitor or a tissue inhibitor of
metalloproteases.
4. A method for inducing and/or stimulating the growth of hair
and/or slowing hair loss comprising applying to the hair and/or the
scalp of an individual in need thereof, a topical composition
comprising at least one chemical inhibitor of metalloproteases
other than chelating calcium ions, and a physiologically acceptable
medium.
5. A method according to claim 4, wherein the chemical inhibitor is
a thiol or a hydroxamate.
6. The method according to claim 1, wherein said at least one
inhibitor is present in an amount of between 0.01% and 5% relative
to the total weight of the composition.
7. The method according to claim 2, wherein said at least one
inhibitor is present in an amount of between 0.01% and 5% relative
to the total weight of the composition.
8. The method according to claim 3, wherein said at least one
inhibitor is present in an amount of between 0.01% and 5% relative
to the total weight of the composition.
9. The method according to claim 4, wherein said at least one
inhibitor is present in an amount of between 0.01% and 5% relative
to the total weight of the composition.
10. The method according to claim 5, wherein said at least one
inhibitor is present in an amount of between 0.01% and 5% relative
to the total weight of the composition.
11. The method according to claim 1, wherein said at least one
inhibitor is present in an amount of between 0.05% and 2% relative
to the total weight of the composition.
12. The method according to claim 2, wherein said at least one
inhibitor is present in an amount of between 0.05% and 2% relative
to the total weight of the composition.
13. The method according to claim 3, wherein said at least one
inhibitor is present in an amount of between 0.05% and 2% relative
to the total weight of the composition.
14. The method according to claim 4, wherein said at least one
inhibitor is present in an amount of between 0.05% and 2% relative
to the total weight of the composition.
15. The method according to claim 5, wherein said at least one
inhibitor is present in an amount of between 0.05% and 2% relative
to the total weight of the composition.
16. The method according to claim 1, further comprising leaving
said composition in contact with the hair and/or the scalp for a
sufficient time and optionally rinsing said composition from the
treated area.
17. The method according to claim 2, further comprising leaving
said composition in contact with the hair and/or the scalp for a
sufficient time and optionally rinsing said composition from the
treated area.
18. The method according to claim 3, further comprising leaving
said composition in contact with the hair and/or the scalp for a
sufficient time and optionally rinsing said composition from the
treated area.
19. The method according to claim 4, further comprising leaving
said composition in contact with the hair and/or the scalp for a
sufficient time and optionally rinsing said composition from the
treated area.
20. The method according to claim 5, further comprising leaving
said composition in contact with the hair and/or the scalp for a
sufficient time and optionally rinsing said composition from the
treated area.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of copending U.S. patent
application Ser. No. 10/677,284, filed Oct. 3, 2003, which is a
continuation of U.S. patent application Ser. No. 09/700,195, filed
Feb. 20, 2001, now U.S. Pat. No. 6,645,477, both incorporated by
reference herein in their entireties and relied upon, application
Ser. No. 09/700,195 being the U.S. national phase of International
Application No. PCT/FR99/01124, filed May 11, 1999, published as
WO99/58101 on Nov. 18, 1999, and claiming the priority of
Application No. 98/05968, filed May 12, 1998 in France.
[0002] The present invention relates to the use, in or for the
preparation of a composition, as active principle in a
physiologically acceptable medium, of an effective amount of at
least one metalloprotease inhibitor, or of any functional
biological equivalent, which is intended to induce and/or stimulate
the growth of head hair or other hairs and/or to slow down their
loss.
[0003] In humans, the growth and renewal of the hair are mainly
determined by the activity of the hair follicles and by their
dermo-epidermal environment. Their activity is cyclic and
essentially comprises three phases, i.e. the anagenic phase, the
catagenic phase and the telogenic phase.
[0004] The active anagenic phase or growth phase, which lasts for
several years and during which the hair gets longer, is followed by
a very short and transient catagenic phase which lasts a few weeks,
and then comes a rest phase, known as the telogenic phase, which
lasts a few months.
[0005] At the end of the rest period, the hair falls out and
another cycle begins. The head of hair is thus under constant
renewal, and out of the approximately 150,000 hairs which make up a
head of hair, at any given moment, approximately 10% of them are at
rest and will thus be replaced within a few months.
[0006] In a large number of cases, early hair loss occurs in
individuals who are genetically predisposed, and it usually affects
men. This more particularly concerns androgenetic or androgenic or
even androgenogenetic alopecia.
[0007] This alopecia is essentially due to a disruption in hair
renewal which leads, in a first stage, to an acceleration of the
frequency of the cycles, at the expense of the quality of the hair
and then at the expense of its quantity. A gradual depletion of the
head of hair takes place by regression of the so-called "terminal"
hairs at the downy stage. Regions are preferentially affected, in
particular the temples or frontal bulbs and the back of the head in
men, while in women diffuse alopecia of the vertex is observed.
[0008] Substances for suppressing or reducing alopecia, and in
particular for inducing or stimulating hair growth or reducing hair
loss, have been sought for many years in the cosmetics and
pharmaceutical industries.
[0009] Admittedly, in this respect, a large number of very diverse
active compounds have already been proposed, such as, for example,
2,4-diamino-6-piperidinopyrimidine 3-oxide or "Minoxidil" described
in U.S. Pat. No. 4,596,812, or the many derivatives thereof, such
as those described, for example, in patent applications 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. Mention may also be made of
6-amino-1,2-dihydro-1-hydroxy-2-imino-4-piperidinopyrimidine and
its derivatives, which are described more particularly in U.S. Pat.
No. 4,139,619.
[0010] However, it would generally still be advantageous and useful
to be able to provide active compounds other than those already
known.
[0011] Now, after considerable research conducted in this matter,
the Applicant has just discovered that a metalloprotease inhibitor,
or any functional biological equivalent, makes it possible to
induce and/or stimulate the growth of head hair or other hairs,
and/or to reduce their loss in an effective manner.
[0012] Metalloproteases (MMPs) are members of a family of
proteolitic enzymes (endoproteases) which contain a zinc atom
co-ordinated to 3 cysteine residues and one methionine residue in
their active site and which degrade the macromolecular components
of the extracellular matrix and the basal sheets at neutral pH
(collagen, elastin, etc.). These enzymes, which are very widely
distributed in the living world, are present, but weakly expressed,
in normal physiological situations such as organ growth and tissue
renewal. However, their overexpression in man and their activation
are associated with many processes which involve the destruction
and remodelling of the matrix. This entails, for example, an
uncontrolled resorption of the extracellular matrix.
[0013] Metalloproteases are produced and secreted in an inactive
zymogenic form (pro-enzyme). These zymogenic forms are then
activated in the extracellular environment by the removal of a
propeptide region. The members of this family can activate each
other.
[0014] Regulation of the activity of MMPs thus takes place at the
level of the expression of the genes (transcription and
translation), at the level of the activation of the zymogenic form,
or at the level of the local control of the active forms.
[0015] The main regulators of the activity of MMPs are the tissue
inhibitors of metalloproteases, or TIMPs. However, the expression
of MMPs is also modulated by growth factors, cytokines, oncogenic
products (ras, jun) or matrix constituents.
[0016] The metalloprotease family consists of several well-defined
groups based on their resemblances in terms of substrate
specificity and structure (see Woessner J. F., Faseb Journal, vol.
5, 1991, 2145). Among these groups, mention may be made of
collagenases intended to degrade fibrillar collagens (MMP-1 or
interstitial collagenase, MMP-8 or neutrophil collagenase, and
MMP-13 or collagenase 3), gelatinases which degrade type IV
collagen or any form of denatured collagen (MMP-2 or gelatinase A
(72 kDa), MMP-9 or gelatinase B (92 kDa)), stromelysins whose broad
spectrum of activity applies to extracellular matrix proteins such
as glycoproteins (fibronectin, laminin), proteoglycans, etc. or
alternatively membrane metalloproteases.
[0017] The Applicant has now discovered that metalloproteases are
present in the internal structures of hair follicles, namely in the
inner epithelial sheath (IRS). In particular, MMP-9 is found in the
IRS.
[0018] Now, it is known that in the course of the hair cycle, hair
follicles pass from a low-level location in the dermis in the
anagenic phase, to a high-level location in the dermis during the
telogenic phase. This movement should be accompanied by a change in
the extracellular matrix which allows the migration of the
follicle, this change possibly being due to an expression of the
MMPs, bringing about a controlled degradation of the said
extracellular matrix. It is at the end of the telogenic phase that
hair loss occurs. However, it is also known that cytokines and
growth factors have an influence on the hair cycle. For example,
epidermal growth factor (EGF) promotes the in vitro transition from
the anagenic phase to the catagenic phase (formation of a "club"
structure characteristic of the catagenic phase), this being the
phase which precedes the loss of the head hairs or other hairs. It
is also known, as the Applicant has demonstrated, that there is an
inflammatory phase in alopecia.
[0019] The Applicant has shown that the MMPs and particularly
MMP-9, can be induced by interleukin-1 and/or EGF, in particular in
the fibroblasts of the dermal papillae.
[0020] The advantage of reducing the expression of MMPs in the
scalp in order to slow down or inhibit the degradation of the
perifollicular matrix and thus to slow down or even prevent hair
loss may thus be appreciated.
[0021] The Applicant thus proposes the use of metalloprotease
inhibitors to induce and/or stimulate the growth of head hair or
other hairs and/or to slow down their loss.
[0022] Thus, the invention relates to the use, in or for the
preparation of a composition, of an effective amount of at least
one metalloprotease inhibitor or of any functional biological
equivalent, which is intended to induce and/or stimulate the growth
of head hair or other hairs and/or to slow down their loss.
[0023] The expression "functional biological equivalent" means any
molecule which is functionally equivalent in terms of biological
function, at least one of the components of which may have been
changed for an equivalent component.
[0024] Examples which may be mentioned are peptides, one biological
equivalent of which may be a peptide in which at least one amino
acid residue has been replaced with another amino acid having a
similar hydropathic index.
[0025] The expression "metalloprotease inhibitor" means any
molecule capable of regulating the activity of MMPs either at the
level of the expression of the genes (transcription and
translation) or at the level of the activation of the zymogenic
form of MMPs, or alternatively at the level of the local control of
the active forms.
[0026] The main regulators of the activity of MMPs are natural
molecules present in the tissues, known as tissue inhibitors of
metalloproteases, or TIMPs.
[0027] However, these inhibitors may also be known chemical
molecules such as, for example, hydroxamic acid derivatives,
cation-chelating agents, growth factors, cytokines, oncogenic
products (ras, jun) or matrix constituents.
[0028] According to the invention, tissue inhibitors of
metalloproteases (TIMPs) such as, for example, the peptides known
in the prior art under the names TIMP-1, TIMP-2, TIMP-3 and TIMP-4
(Woessner J. F., Faseb Journal, 1991) are preferably used.
[0029] Thus, the invention relates more particularly to the use, in
or for the preparation of a composition, of an effective amount of
at least one tissue inhibitor of metalloproteases (TIMP) or of any
functional biological equivalent, the inhibitor or the composition
being intended to induce and/or stimulate the growth of head hair
or other hairs and/or to slow down their loss.
[0030] The peptides known in the prior art under the names TIMP-1,
TIMP-2, TIMP-3 and TIMP-4 are preferably used according to the
invention as tissue inhibitors of metalloproteases.
[0031] Needless to say, according to the invention, the
metalloprotease inhibitors can be used alone or as a mixture.
[0032] It may be the case that, for reasons of resistance to
degradation, it is necessary according to the invention to use a
protected form of the metalloprotease inhibitor. The form of the
protection should obviously be a biologically compatible form. Many
biologically compatible forms of protection may be envisaged, such
as, for example, acylation or acetylation of the amino-terminal end
or amidation of the carboxy-terminal end.
[0033] Thus, the invention relates to a use as defined above,
characterized in that the metalloprotease inhibitor is in a
protected or unprotected form.
[0034] A protection based either on the acylation or acetylation of
the amino-terminal end, or on the amidation of the carboxy-terminal
end, or alternatively on both approaches, is preferably used
according to the invention.
[0035] Among the chemical inhibitors which may be mentioned are
thiols and hydroxamates.
[0036] The amount of metalloprotease inhibitor which can be used
according to the invention obviously depends on the desired effect
and should be in an amount which is effective to induce and/or
stimulate the growth of head hair or other hairs and/or to slow
down their loss.
[0037] By way of example, the amount of metalloprotease inhibitor
which can be used according to the invention may range, for example
from 0.01% to 5% and preferably from 0.05% to 2% relative to the
total weight of the composition.
[0038] The composition is preferably a cosmetic composition.
[0039] The composition according to the invention can be
administered enterally or parenterally. Preferably, via the
parenteral route, the composition is administered topically.
[0040] The physiologically acceptable medium in which the peptide
is used according to the invention may be anhydrous or aqueous. The
expression "anhydrous medium" means a solvent medium containing
less than 1% water. This medium may consist of a solvent or a
mixture of solvents chosen more particularly from C.sub.2-C.sub.4
lower alcohols such as ethyl alcohol, alkylene glycols such as
propylene glycol, and alkylene glycol alkyl ethers or dialkylene
glycol alkyl ethers, the alkyl or alkylene radicals of which
contain from 1 to 4 carbon atoms. The expression "aqueous medium"
means a medium consisting of water or of a mixture of water and
another physiologically acceptable solvent, chosen in particular
from the organic solvents mentioned above. In this last case, when
these other solvents are present, they represent approximately 5%
to 95% by weight of the composition.
[0041] It is possible for the physiologically acceptable medium to
contain other adjuvants usually used in cosmetics, such as
surfactants, thickeners or gelling agents, cosmetic agents,
preserving agents, and acidifying and basifying agents that are
well known in the prior art, and in amounts that are sufficient to
obtain the desired presentation form, in particular a more or less
thickened lotion, a gel, an emulsion or a cream. The composition
can optionally be used in a form pressurized as an aerosol or
vaporized from a pump-dispenser bottle.
[0042] It is also possible for the peptide to be used in
combination with compounds for further improving the activity on
hair regrowth and/or on slowing down hair loss, which have already
been described for this activity.
[0043] Among the latter compounds, mention may be made more
particularly, in a non-limiting manner, of:
[0044] nicotinic acid esters, in particular including tocopheryl
nicotinate, benzyl nicotinate and C.sub.1-C.sub.6 alkyl nicotinates
such as methyl or hexyl nicotinate;
[0045] pyrimidine derivatives, such as
6-amino-1,2-dihydro-1-hydroxy-2-imino-4-piperidinopyrimidine also
known as "Minoxidil" and as described in U.S. Pat. No.
4,139,619;
[0046] antiandrogenic agents
[0047] 5-reductase inhibitors;
[0048] OH-radical scavengers, such as dimethylsulfoxide;
[0049] peptides such as, for example, the tripeptide
Lys-Pro-Val;
[0050] microorganism extracts, particularly bacterial extracts;
[0051] plant extracts.
[0052] Other compounds can also be added to the above list, namely,
for example, phospholipids such as lecithin, linoleic acid,
linolenic acid, salicylic acid and derivatives thereof described in
French patent FR 2 581 542, for instance salicylic acid derivatives
bearing an alkyl radical containing from 2 to 12 carbon atoms in
position 5 of the benzene ring, hydroxycarboxylic or ketocarboxylic
acids and esters thereof, lactones and the corresponding salts
thereof, carotenoids, eicosatetraenoic and eicosatrienoic acids or
esters and amides thereof, vitamin D and derivatives thereof.
[0053] The cosmetic composition according to the invention can be
applied to the alopecic regions of the scalp and hair of an
individual, and is optionally left in contact for several hours and
is optionally to be rinsed out. For example, the cosmetic
composition containing an effective amount of at least one
metalloprotease inhibitor can be applied to the hair and the scalp
in the evening, kept in contact throughout the night and optionally
shampooed out in the morning. These applications can be repeated
daily for one or more months depending on the individual.
[0054] Thus, a subject of the present invention is also a cosmetic
process for treating the hair and/or the scalp, characterized in
that it consists in applying a cosmetic composition containing an
effective amount of at least one metalloprotease inhibitor to the
hair and/or the scalp, in leaving this composition in contact with
the hair and/or the scalp, and optionally in rinsing it off.
[0055] The treatment process has the characteristics of a cosmetic
process since it improves the aesthetics of the hair by making it
more vigorous and making it look better.
[0056] Examples will now be given by way of illustration, which
should not in any way limit the scope of the invention.
EXAMPLE I
[0057] An example of a daily lotion is as follows: TABLE-US-00001
TIMP-1 0.01 g TIMP-2 0.01 g 2,4 Diaminopyrimidine 3-oxide 0.75 g
95.degree. ethanol 30 g Fragrance qs Dyes qs Demineralized water qs
100 g
EXAMPLE 2
[0058] An example of a liposomal gel is as follows: TABLE-US-00002
Natipide II.sup.1 (i.e. 2 g of phospholipids) 10 g TIMP-2 0.025 g
Carbomer 0.25 g Triethanolamine qs pH = 7 Preserving agents qs
Demineralized water qs 100 g .sup.1Water/Alcohol/Lecithin mixture
from the company Nattermann
* * * * *