Drug – bio-affecting and body treating compositions – Live hair or scalp treating compositions
Reexamination Certificate
2001-02-20
2003-11-11
Henley, III, Raymond (Department: 1614)
Drug, bio-affecting and body treating compositions
Live hair or scalp treating compositions
C435S069200, C435S069100, C435S183000
Reexamination Certificate
active
06645477
ABSTRACT:
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.
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.
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.
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.
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.
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, whilst in women diffuse alopecia of the vertex is observed.
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.
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 1hydroxy-2-imino-4-piperidinopyrimidine and its derivatives, which are described more particularly in patent U.S Pat. No. 4,139,619.
However, it would generally still be advantageous and useful to be able to provide active compounds other than those already known.
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.
Metalloproteases (MMPs) are members of a family of proteolitic enzymes (endoproteases) which contain a zinc atom coordinated 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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
Jarrousse Francoise
Mahe Yann
Burns Doane Swecker & Mathis L.L.P.
Henley III Raymond
Jagoe Donna
Societe L'Oreal S.A.
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