Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2000-07-14
2003-04-01
Padmanabhan, Sreeni (Department: 1617)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C424S401000, C514S038000, C548S454000, C548S516000, C252S380000
Reexamination Certificate
active
06541507
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Technical Field of the Invention
The present invention relates to the administration of an effective amount of 4,6-dimethoxyindole-2-carboxylic acid or derivative or composition comprised thereof, to induce and/or stimulate hair growth and/or to prevent hair loss.
2. Description of the Prior Art
In human subjects, the growth and renewal of the hair are principally determined by the activity of the hair follicles. This 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 becomes longer, is followed by a very short and transient catagenic phase which lasts a few weeks, and then a rest or quiescent 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 on a human head of hair, at any given moment, approximately 10% of them are at rest and will thus be replaced within a few months.
However, different causes can lead to a considerable, temporary or permanent, loss of hair. Alopecia is essentially due to a disruption in hair renewal which gives rise, 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 in men, and in women diffuse alopecia of the vertex is observed.
The term “alopecia” is generic to the entire family of afflictions of the hair follicle, the final consequence of which is the partial or general permanent loss of the hair. In a large number of cases, early loss of the hair occurs in genetically predisposed individuals and especially is prevalent in men. This ie more particularly the case as regards androgenetic or androgenic or even androgeno-genetic alopecia.
Active agents for suppressing or reducing alopecia, and in particular for inducing or stimulating hair growth or reducing hair loss, have long been considered desiderata in the cosmetics and pharmaceutical industries.
In this respect, a large number of very diverse active compounds have already been proposed for such purposes, for example, 2,4-diamino-6-piperidino-pyrimidine 3-oxide or “Minoxidil” as described in U.S. Pat. Nos. 4,139,619 and 4,596,812, or the many derivatives thereof, such as those described, for example, in 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.
Specific compounds of the indolecarboxylic family, such as those described in WO-A-99/12905, have also been proposed for their ability to induce and/or stimulate hair growth and/or to prevent hair loss.
These compounds exhibit pronounced inhibitory activity on type I and type II 5&agr;-reductases, which, according to the theory which considers that these proteins are involved in hair loss, makes them excellent candidates as active principles for inducing and/or stimulating hair growth and/or for preventing hair loss.
However, 5&agr;-reductases are not exclusively present in the hair follicles, and the value of providing compounds suited for inducing and/or stimulating hair growth and/or of preventing hair loss, but which have no activity on type I and II 5&agr;-reductases, consequently, can readily be appreciated.
SUMMARY OF THE INVENTION
It has now surprisingly and unexpectedly been determined that 4,6-dimethoxyindole-2-carboxylic acid and derivatives thereof have the property of inducing and/or stimulating hair growth and/or of preventing hair loss, but do not exhibit any activity on type I and type II 5&agr;-reductases.
Briefly, the present invention features cosmetic/dermatological compositions comprising a therapeutically effective amount of at least one compound having the structural formula (I):
in which R
1
and R
2
, which may be identical or different, are each a hydrogen atom; a C
1
-C
6
alkyl radical, optionally substituted with an —OH, —NHR
3
, —SH, —COOH or —COOR
3
radical, in which R
3
is a linear or branched C
1
-C
4
alkyl radical; a C
7
-C
12
aralkyl radical; or a radical —CHR
4
R
5
, wherein R
4
and R
5
, which may be identical or different, are each a hydrogen atom, an optionally substituted phenyl radical, or a 5- or 6-membered heterocycle; the acylated derivatives or the physiologically acceptable salts thereof, either singly or in any admixture in any proportion; said compound and/or said compositions being well suited to induce and/or stimulate hair growth and/or to prevent hair loss.
DETAILED DESCRIPTION OF BEST MODE AND SPECIFIC/PREFERRED EMBODIMENTS OF THE INVENTION
More particularly according to the present invention, the subject compounds exhibit marked utility as active principles for inducing and/or stimulating hair growth and/or for preventing hair loss.
It was hitherto unknown to administer such compounds for combating hair loss.
According to the invention, by the term “heterocycle” is preferably intended a ring optionally including one or more nitrogen and/or oxygen atoms, and particularly pyridine, imidazole, tetrahydrofuran or furan. One heterocycle which is particularly preferred according to the invention is pyridine.
By the expression “C
1
-C
4
alkyl radical” are intended linear or branched acyclic radicals having from 1 to 4 carbon atoms, derived from the removal of a hydrogen atom from a hydrocarbon molecule, and in particular methyl, ethyl, propyl, isopropyl, butyl, isobutyl or tert-butyl radicals.
By the expression “C
7
-C
12
aralkyl radical” are preferably intended alkylaryl radicals containing from 7 to 12 carbon atoms, in which definition the term “aryl” connotes an aromatic ring containing 5 or 6 carbon atoms or an aromatic heterocycle containing 5 or 6 atoms. According to the invention, the aralkyl radical is preferentially C
7
-C
10
. One aralkyl radical which is particularly preferred according to the invention is the benzyl radical.
And by the expression “optionally substituted phenyl radical” is preferably intended a phenyl radical optionally substituted with a cyano (—CN) group, a trifluoromethyl (—CF
3
) group, a methoxy (—O—CH
3
) radical or a halogen atom. The halogen atom can be selected from among chlorine, bromine, fluorine and iodine. One substituted phenyl radical which is particularly preferred according to the invention is a phenyl radical substituted with a trifluoromethyl (—CF
3
) group.
In one preferred embodiment of the invention, R
1
is a hydrogen atom or a methyl or ethyl radical.
In another preferred embodiment of the invention, R
2
is a hydrogen atom or a methyl radical.
And in a very preferred embodiment of the invention, R
1
and R
2
are each a hydrogen atom.
Exemplary compounds of formula (I) include:
4,6-dimethoxyindole-2-carboxylic acid;
methyl 4,6-dimethoxyindole-2-carboxylate;
N-methyl-4,6-dimethoxyindole-2-carboxylic acid;
methyl N-methyl-4,6-dimethoxyindole-2-carboxylate;
N-ethyl-4,6-dimethoxyindole-2-carboxylic acid.
Among these compounds, that most particularly preferred is 4,6-dimethoxyindole-2-carboxylic acid.
According to the invention, the subject compounds can be used alone or as a mixture.
It will of course be appreciated that the effective amount of compound to be administered corresponds to the amount required to elicit the desired result. One skilled in this art is thus capable of evaluating this effective amount, which depends on the nature of the compound and on the person thus treated. To provide an order of magnitude, in the compositions according to the invention the compound of formula (I) is typically present at a concentration ranging from 0.3% to 30% by weight relative to the total weight of the composition and preferably from 0.5% to 20%.
According to the invention, the compounds of formula (I) can be formulated
Bernard Bruno
Dalko Maria
Galey Jean-Baptiste
Burns Doane Swecker & Mathis L.L.P.
Padmanabhan Sreeni
Societe L'Oreal S.A.
Willis Michael A.
LandOfFree
Indolecarboxylic compounds for inducing/stimulating hair... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Indolecarboxylic compounds for inducing/stimulating hair..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Indolecarboxylic compounds for inducing/stimulating hair... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3030067