FR2753375A1 - Compositions for retarding or inhibiting hair growth - Google Patents

Abstract

The use of a sulphotransferase inhibitor (I) is claimed in a cosmetic composition, or in the preparation of a medicament, for retarding or inhibiting the growth of hair. Also claimed are: (I)-containing compositions for use as above; products for use as above, containing (I) and another active agent for simultaneous, separate or sequential use; and corresponding treatment methods.

Description

USE IN A COSMETIC COMPOSITION OR FOR
PREPARATION OF A MEDICAMENT OF AT LEAST ONE INHIBITOR OF
sulfotransferase
The present invention relates, in its most general aspect, to the use in a cosmetic composition or for the preparation of a medicament for slowing or preventing the growth of hair and / or hair of at least one sulfotransferase inhibitor.

It also relates to various types of compositions that can be used according to the invention as well as a non-therapeutic treatment method for modifying hair growth.

It is known that the metabolism of drugs and xenobiotics is one of the essential roles of the sulfation (or sulfo-conjugation) reactions that take place in the cells of the tissues of the human body.

The enzymes responsible for this sulphation are mainly located in the liver where their role is detoxification. These enzymes are found in other tissues such as the skin. These sulfotransferases are able to catalyze the sulphation of a wide range of substrates such as for example sugar residues of glycoproteins or glycosaminoglycans, tyrosines in peptides or proteins, sulpholipids, steroids, catecholamines or all kinds of drugs or xenobiotics.

Sulfotransferases are a family of enzymes that include membrane-associated enzymes, especially those capable of conjugating proteins or glycosaminoglycans, and enzymes in soluble form generally associated with sulfation of drugs and / or xenobiotics, or even compounds endogenous drugs such as steroids, thyroid hormones, bile acids and monoamino neurotransmitters.

Three isoenzymes have been isolated so far, two are phenols sulfotransferases (M-PST or monoamine-sulfating phenol sulfotransferases and
P-PST or phenol-sulfating phenol sulfotransferase) and one is a sulfotransferase acting more particularly on bile acids and steroids (DHEA-ST or dehydroepiandrosterone sulfotransferase).

 Up to now, no direct relationship has been made between the presence of sulfotransferases in skin cells and the growth of hair and / or hair.

Now, after extensive research, it has now been found by the
It can be established that a relationship between sulfotransferases and inhibition of hair and / or hair growth can be established and that by inhibiting (according to techniques described below) the activity of sulfotransferases within the skin, one could, quite unexpectedly and surprisingly, substantially modify the growth of hair and / or hair.

More specifically, it has been found that by inhibiting the activity of sulfotransferases, it is possible to slow down and / or prevent the growth of hair and / or hair.

This discovery is the basis of the present invention.

In the following description of the present invention is meant:
by a sulfotransferase "inhibitor", any substance which, in vitro, makes it possible to limit or completely inhibit the enzymatic activity of sulfotransferases, or any substance presenting a positive response in the tests described by Mulder and Scholteer (Biochem. 1997), 165, 553-559) or by Beckmann (Anal.

Biochem. (1991), 197, 408-411), or Sekura and Jakohy (J. Biol Chem (1979), 254, 5658-5663);
- "Topical", any technique of administering a product by direct application of the latter on a superficial (or external) part of the body, such as skin, hair and others;
- By "systemic", any technique of administering a product by a route other than topical, for example oral and / or parenteral.

Thus, according to a first aspect of the present invention, it is now proposed the use in a cosmetic composition or for the preparation of a medicament for slowing down and / or preventing the growth of hair and / or hair, for use in less a sulfotransferase inhibitor.

According to finally other aspects of the present invention, it is also proposed compositions or associations, new in themselves, that can be used according to the invention taken in these various variants.

Other features, aspects, objects and advantages of the invention will appear even more clearly on reading the description which follows, as well as various concrete examples, but not limiting, intended to illustrate it.

We will begin by detailing, in their nature, the various products and compositions used in the context of the present invention.

The inhibitory nature of a given substance with respect to sulfotransferases can be classically determined by those skilled in the art by means in particular of the usual biochemical tests, such as those mentioned above.

The sulfotransferase inhibitors may be chosen especially from phenols, diethylcarbamazine, benzyl alcohols, arylcarboxylic acids, salicylic acid derivatives, orthohydroxyarylaldehydes, sodium citrate, α-hydroxyacids, sodium chlorate, and chloride. ammonium, cell anion transport inhibitors such as anionic amphiphilic compounds, non-sulfated phosphoadenosine phosphosulphate analog (PAPs) nucleotides, flavonoids, curcumin, ellagic acid, or those described by tlortin (Biochem. Biophys.

Res. Comm., (1998), 150: 1, 342-348).

Among the phenols that may be mentioned are chlorophenol, pentachlorophenol, acetylaminophenol or acetaminophen, 2,6-dichloro-4-nitrophenol or alternatively t3-naphthol.

Among the benzyl alcohols include those described by Rao (Chirality, (1991), 3, 104-111).

Among the arylcarboxylic acids, mention may be made of 1-naphthoic acid, naphthoic acid 2, naphthaldehydes or naphthalenemethanols (Duffel MW, Drug).
Metab. & Available (1993), 21: 2, 400402).

Among the salicylic acid derivatives that may be mentioned are sodium salicylate, salicylamide and salicylaldehydes.

Among the inhibitors of cellular transport of anions, mention may be made of flufenamic acid or niflumic acid.

Among the non-sulfated analogous nucleotides of phosphoadenosine phosphosulphate mention may be made of adenosine 3'5'-bis phosphate, phosphoadenosine phosphate or the 2'3 'dialdehydes of ribonucleotides.

Flavonoids include quercetin, fisetin, galangin, myricetin, chrysin, apigenin or kaempferol.

Finally, it will generally be noted that, in the context of the present invention, it is of course entirely possible to use mixtures of inhibitors, provided of course that these mixtures remain compatible with the desired effect.

The amount of inhibitor that can be used according to the invention is of course dependent on the desired effect. It also depends on the inhibitor. It can therefore vary to a large extent.

To give an order of magnitude, if a sulfotransferase inhibitor is used in a cosmetic composition, it may contain the inhibitor in an amount representing from 0.1% to 5% of the total weight of the composition and preferably in an amount representing 1 the non-sulfated analog nucleotides of phosphoadenosine phosphosulfate at 2% of the total weight of the composition.

To give an order of magnitude, if a sulfotransferase inhibitor is used for the preparation of a drug, it may contain the inhibitor in an amount representing 1% to 15% of the total weight of the composition and preferably in an amount representing from 5% to 10% of the total weight of the composition.

In general, it will be noted that all the above products may be conventionally packaged in a form that is suitable for the mode of administration or application used for the latter (lotions, shampoos, tablets, syrups, nutritional supplements and others). .

The compositions within the scope of the present invention are more particularly compositions comprising at least one sulfotransferase inhibitor.

As indicated above, each of the compositions are conventionally packaged in a form that is suitable for the various modes of administration or application envisaged (lotions, shampoos, tablets, syrups and others). Thus, the compositions are preferably packaged in a form suitable for topical application.

The compositions according to the invention can also make use of various conventional and customary additives, in particular cosmetics in the case of topical applications (hair products in particular), chosen, for example, from filters
UV, thickening agents, penetrating agents such as urea, organic solvents such as ethanol, isopropanol, alkylene glycols, surfactants chosen from nonionic surfactants such as alkylpolyglycosides, cationic surfactants , anionic surfactants and amphoteric surfactants, dyes, anti-dandruff agents, perfumes and preservatives.

 It is also possible to incorporate into the compositions according to the invention products already known to have an activity in the field of slowing down and / or inhibition of hair growth and / or hair growth.

In this regard, for example, cyclooxygenase inhibitors and / or lipoxygenase activators, such as those mentioned in patent applications EP-A-94/402055, WO-A-94/27586 or WO-A- 94127563.

Thus, according to a particular embodiment of the invention, the compositions may further comprise at least one other product capable of slowing down and / or inhibiting the growth of the hairs and / or the hair.

More particularly, the compositions according to the invention may furthermore comprise at least one cyclooxygenase inhibitor and / or at least one lipoxygenase activator at doses of each of inhibitor and / or activator for which they are taken individually. exhibit inhibitory activity of hair growth.

According to yet another embodiment of the invention, the compositions may comprise, in addition to at least one sulfotransferase inhibitor, at least one cyclooxygenase inhibitor and / or at least one lipoxygenase inhibitor.

Indeed, the Applicant has discovered that the combination of a lipoxygenase inhibitor and a cyclooxygenase inhibitor, when they are taken at doses of each of the inhibitors for which they individually do not present any activity or conversely have a reverse activity, has the power to slow down and / or inhibit the growth of hair and / or hair.

Thus, according to another aspect of the invention, there are provided compositions, new in themselves, comprising at least one sulfotransferase inhibitor, at least one lipoxygenase inhibitor and / or at least one cyclooxygenase inhibitor, these inhibitors being at doses for which they individually have no activity or stimulating activity of the shoot.

Whatever the composition envisaged, it is possible to combine in a single composition the sulfotransferase inhibitor and the other active component (s) on the growth of hair. However, particular embodiments can be envisaged, in particular the sulfotransferase inhibitor and the other active component (s) can be administered simultaneously, separately or spread over time.

Thus, the subject of the invention is a product comprising at least one sulfotransferase inhibitor and at least one other active component as a combination product for simultaneous, separate or spreading use over time to slow down and / or inhibit the growth of hair and / or hair.

In a particular embodiment, the sulfotransferase inhibitor and the other active ingredient (s) may be separately packaged as a kit whose components will be mixed extemporaneously.

The subject of the invention is thus a kit comprising at least one sulfotransferase inhibitor and at least one other active component for simultaneous, separate or spread use over time to slow down and / or inhibit the growth of the hairs and / or the hair.

According to the invention, the lipoxygenase inhibitor may be used in an amount ranging from 0.01% to 5% by weight, preferably ranging from 0.1% to 1% and even more preferentially ranging from 0.1% to 0.8%.

Likewise, the cyclooxygenase inhibitor may be used in an amount of from 0.001% to 5% by weight and preferably from 0.01% to 0.1%.

According to yet another aspect of the present invention, there is also provided a non-therapeutic treatment method for slowing down and / or inhibiting hair and / or hair growth which essentially consists in administering to
The organism, topically and / or systemically, at least one sulfotransferase inhibitor, at doses as defined above.

Preferably, the sulfotransferase inhibitor is administered topically.

According to a particularly preferred embodiment of the method according to the invention, the compositions are applied to the skin and / or the scalp as defined above.

To obtain significant effects, the frequency of administration or application of the compositions according to the invention is of the order of one to two times per day. In this regard, it has been noted that the sufficient quantities of inhibiting agents to be used in the context of the invention can generally remain very low.

The present invention finds particularly useful applications in the field of the treatment of various pathologies affecting the skin and / or the scalp, in particular hirsutism.

Concrete examples illustrating the invention will now be given.

Example 1 Effect of 2,6-dichloro-4-nitrophenol on the growth of the hairs.

C57BL6 mice, 42-day old males, are selected for their resting hair cycle. They are then shaved. The synthesis of melanin intervenes only on hairs in active phase, the skin of the shaved mice is pink.

The animals are divided into two groups, one receiving 2,6-dichloro-4-nitrophenol, the other not being treated.

2,6-dichloro-4-nitrophenol is administered intraperitoneally at 26 Fmol / kg in physiological saline. The administration takes place twice a week for 2 weeks starting on the day of shaving.

The animals are observed daily and we note the percentage of animals for which the shoot started (appearance of the smallest gray spot on the surface of the shaved skin) and the percentage of animals for which the hair is growing longer.

The results are given in the following table.

<tb><SEP> PUSH <SEP> ELONGATION
<tb> DAYS <SEP> WITNESS <SEP> 2,6-D <SEP> WITNESS <SEP> 2,6-D
<tb><SEP> 3 <SEP> 0.0 <SEP> 0.0 <SEP> 0.0 <SEP> 0.0
<tb><SEP> 4 <SEP> 5.3 <SEP> 0.0 <SEP> 0.0 <SEP> 0.0
<tb><SEP> 5 <SEP> 10.5 <SEP> 5.0 <SEP> 5.3 <SEP> 0.0
<tb><SEP> 6 <SEP> 15.8 <SEP> 5.0 <SEP> 5.3 <SEP> 0.0
<tb><SEP> 7 <SEP> 31.6 <SEP> 5.0 <SEP> 5.3 <SEP> 0.0
<tb><SEP> 8 <SEP> 57.9 <SEP> 15.0 <SEP> 15.8 <SEP> 5.0
<tb><SEP> 9 <SEP> 78.9 <SEP> 25.0 <SEP> 26.3 <SEP> 5.0
<tb><SEP> 10 <SEP> 89.5 <SEP> 50.0 <SEP> 68.4 <SEP> 25.0
<tb><SEP> It <SEP> 94.7 <SEP> 60.0 <SEP> ~ <SEP> 84.2 <SEP> 55.0
<tb><SEP> 12 <SEP> 100.0 <SEP> 70.0 <SEP> 89.5 <SEP> i <SEP> 60.0
<Tb>

2,6-D = 2,6-dichloro-4-nitrophenol
Re-emergence of the shoot and hair extension are significantly delayed in animals receiving 2,6-dichloro-4-nitrophenol compared to untreated animals.

Example 2
Examples of formulations illustrating the invention. These compositions were obtained by simple mixing of the various components.

Composition 1: Non-rinsed lotion 2,6-dichloro-4-nitrophenol 1.0 g
Propylene glycol 22.8 g
Ethanol 95C 55.1 g
Purified water qs 100 g
Composition 2: Rinsed lotion 2,6-dichloro4-nitrophenol 5.0 g
Propylene glycol 22.8 g
Absolute ethanol qs 100 g
Composition 3: Lotion not rinsed
Sodium salicylate 8.0 g
Ethanol 95 "55.1 g
Purified water qs 100 g
Composition 4: Shampoo
Sodium salicylate 5.0 g p-acetylamino phenol 2.0 g surfactant APG 300 15.0 g
Purified water qs 100 g

Claims (16)

 1. Use in a cosmetic composition or for the preparation of a drug of at least one sulfotransferase inhibitor, said composition or said medicament being intended to slow down and / or inhibit the growth of hair and / or hair. 2. Use according to the preceding claim, characterized in that the sulfotransferase inhibitor is administered topically or systemically. 3. Use according to the preceding claim, characterized in that the sulfotransferase inhibitor is administered topically. 4. Use according to any one of the preceding claims, characterized in that the sulfotransferase inhibitor is chosen from phenols, diethylcarbamazine, benzyl alcohols, arylcarboxylic acids, salicylic acid derivatives, orthohydroxyarylaldehydes, sodium citrate, α-hydroxyacids, sodium chlorate, ammonium chloride, cell anionic transport inhibitors such as anionic amphiphilic compounds, non-sulfated phosphoadenosine phosphosulphate analog (PAPs) nucleotides, flavonoids, curcumin, ellagic acid. 5. Use in a cosmetic composition according to any one of the preceding claims, characterized in that the sulfotransferase inhibitor is at a concentration ranging from 0.1% to 5% and preferably from 1% to 2% by weight per relative to the total weight of the composition. 6. Use for the preparation of a medicament according to any one of claims 1 to 4, characterized in that the sulfotransferase inhibitor is at a concentration ranging from 1% to 15% and preferably from 5% to 10% by weight relative to the total weight of the composition. Cosmetic or pharmaceutical composition intended to slow down and / or inhibit the growth of the hairs and / or the hair, characterized in that it comprises as active agent at least one sulphotransferase inhibitor as defined in Claims 2 to 6. . 8. Cosmetic or pharmaceutical composition, characterized in that it comprises at least one sulfotransferase inhibitor as defined in claims 2 to 6 and at least one other product capable of slowing down and / or inhibiting hair growth and / or hair. 9. Composition according to any one of claims 7 or 8, characterized in that it further comprises at least one cyclooxygenase inhibitor and / or at least one lipoxygenase activator. 10. Composition according to any one of claims 7 or 8, characterized in that it further comprises at least one cyclooxygenase inhibitor and / or at least one lipoxygenase inhibitor. 11. Composition according to claim 10, characterized in that the lipoxygenase inhibitor is used in an amount ranging from 0.01% to 5% by weight, preferably ranging from 0.1% to 1% and even more preferably ranging from from 0.1% to 0.8%. 12. Composition according to any one of claims 9 to 11, characterized in that the cyclooxygenase inhibitor can be used in an amount ranging from 0.001% to 5% by weight and preferably ranging from 0.01% to 0.1%. 13. Composition according to any one of claims 7 to 12, used as a medicament for slowing down and / or inhibiting the growth of hair and / or hair. 14. Product comprising at least one sulfotransferase inhibitor as defined in claims 2 to 6 and at least one other product capable of slowing down and / or inhibiting the growth of hair and / or hair as a combination product for simultaneous use , separated or spread over time to slow down and / or inhibit the growth of hair and / or hair. 15. Non-therapeutic treatment method for slowing down and / or inhibiting the growth of hair and / or hair, which essentially consists of administering to the organism, topically and / or systemically, at least one sulfotransferase inhibitor as defined in US Pat. Claims 2 to 6. 16. A non-therapeutic treatment method for slowing down and / or inhibiting the growth of hair and / or hair which essentially consists in administering to The organism, topically and / or systemically, a composition as defined in claims 7 to 13.