Use of salicylic derivatives for the treatment of skin aging

The invention relates to a composition intended for the treatment of skin aging, containing, in a physiologically acceptable medium, at least one salicylic acid derivative corresponding to the formula: ##STR1## in which: R represents a saturated aliphatic chain or an unsaturated chain bearing one or more conjugated or unconjugated double bonds, it being possible for the chains to be substituted with one or more halogen atoms as well as with trifluoromethyl groups, with one or more hydroxyl groups in free form or a form esterified by an acid, or alternatively with a carboxyl group, free or esterified by a lower alcohol; and PA0 R' represents a hydroxyl group or an ester group of formula: ##STR2## where R.sub.1 is a saturated or unsaturated aliphatic group.

The present invention relates to new compositions intended for treating 
skin aging, employing salicylic acid derivatives. 
During the aging process, the appearance on the skin of different signs 
very characteristic of aging, reflected, in particular, in a modification 
of skin structure and function, is observed. These signs are especially 
pronounced on uncovered areas such as face and hands, on which special 
characteristics due to exposure of the skin to sunlight (actinic aging) 
are generally added. 
On an uncovered area, it is difficult, in general, to distinguish clearly 
between signs originating from the physiological process of skin aging and 
signs due to repeated exposure of the skin to light. 
The main clinical signs of skin aging are the following: appearance of deep 
wrinkles, increasing with age. A disorganization of the "grain" of the 
skin is noted, that is to say the micro-relief is less regular and is 
anisotropic in nature. 
The skin color is generally modified, appearing paler and yellower, which 
appears to be due chiefly to a disorganization of the microcirculation 
(less haemoglobin in the papillary layer of the dermis). Numerous colored 
spots appear at the surface, which is due to impaired melanogensis. On 
some areas, diffuse irritation and sometimes telangiectasia are present. 
Another clinical sign of aging is the dry and rough appearance of the skin, 
which is due chiefly to greater desquamation, these squamae contributing 
also to the somewhat grey appearance of the color by diffracting light 
rays. 
Finally, a loss is noted in firmness and tonus of the skin, which, as in 
the case of wrinkles, is explained at least partially by a dermal and 
epidermal atrophy as well as a flattening of the dermoepidermal formation. 
It is hence noted that the clinical signs of skin aging result chiefly from 
a dysfunction of the main biological mechanisms operating in the skin. 
The applicant discovered, surprisingly, that the use of salicylic acid 
derivatives enabled this aging to be retarded and the clinical signs of 
the latter to be effected. 
They found, more especially, that, by means of these salicylic derivatives, 
it was possible to lessen wrinkling at least, to modify the color of the 
skin, which appears more pinkish, to obliterate surface pigmented spots, 
to eliminate squamae and to give a more elastic consistency to the skin. 
It was found, in particular, that it was possible to impart a much softer 
feel to the skin. 
The salicylic acid derivatives which are usable according to the invention 
are known per se, and have already been described in the prior art as 
capable of being used in topical compositions in the field of cosmetology 
and dermopharmacy, and more especially as therapeutic and comedolytic 
agents such as those for the treatment of acne. 
The applicants have now discovered a new therapeutic application acting on 
a biological mechanism completely different from that of acne, which is 
mainly encountered in young individuals. 
The subject of the invention is hence mainly the use of salicylic acid 
derivatives for the treatment of skin aging. 
Another subject of the invention consists of the compositions employed. 
Other subjects of the invention will become apparent on reading the 
description and examples which follow. 
The salicylic acid derivatives which are usable according to the invention 
for the treatment of skin aging correspond essentially to the following 
general formula: 
##STR3## 
in which: 
R represents a linear, branched or cyclized saturated aliphatic chain 
having from 3 to 11 carbon atoms, or an unsaturated chain having from 3 to 
17 carbon atoms, bearing one or more conjugated or unconjugated double 
bonds, it also being possible for the above chains to be substituted with 
one or more halogen atoms as well as with trifluoromethyl groups, with one 
or more hydroxyl groups in free form or a form esterified by an acid 
having from 1 to 6 carbon atoms, or alternatively with a carboxyl group, 
free or esterified by a lower alcohol having from 1 to 6 carbon atoms, it 
being possible for these different groups to be present simultaneously on 
the said substituents; and 
R' represents a hydroxyl group or an ester group corresponding to the 
formula: 
##STR4## 
in which R.sub.1 is a saturated or unsaturated aliphatic group having from 
1 to 18 carbon atoms. 
More especially preferred compounds are those corresponding to the formula 
(I) above in which R' denotes a hydroxyl group and R an alkyl group having 
from 3 to 11 carbon atoms. 
Other especially advantageous compounds are those in which R represents a 
chain derived from linoleic, linolenic or oleic acid. 
Another group of especially preferred compounds consists of the compounds 
in which R denotes an alkyl chain having from 3 to 11 carbon atoms and 
bearing a free, esterified or salified carboxyl group and R' denotes a 
hydroxyl group. 
Especially advantageous compounds according to the invention are selected 
from 5-n-octanoylsalicylic acid, 5-n-dodecanoylsalicylic acid and 
5-n-decanoylsalicylic acid, it being possible for these compounds to be 
optionally used in micronized form. 
Trials performed by the applicants have enabled it, in particular, to be 
shown that the compounds according to the invention have an especially 
exceptional angiogenic effect. 
It is found that application of the composition based on 
5-n-octanoylsalicylic acid produces a large increase in capillary volume 
and number. 
The compositions, used according to the invention in the treatment of skin 
aging, contain at least one salicylic acid derivative of the formula (I) 
defined above in a physiologically acceptable medium, and are generally 
presented in the form of gels, creams, lotions, sticks, foams or soaps, or 
may be pressurized in aerosol devices. 
They can contain water and/or solvents compatible with the skin, for 
example C.sub.1 -C.sub.4 lower alcohols such as ethanol and isopropanol, 
or polyhydric alcohols such as propylene glycol and glycerol, these 
solvents being present in proportions of between 5 and 99% by weight. 
They may also be presented in the form of fatty compositions containing 
oils or fats such as vaseline and triglycerides. 
The compound of formula (I) according to the invention is preferably 
present in these compositions in proportions of between 0.1 and 10% by 
weight. 
These compositions can also contain thickeners, demulcents, superfatting 
agents, emollients, wetting agents, surfactants, preservatives, antifoams, 
sunscreens, oils, waxes, colorings and/or pigments whose function is to 
color the skin or the composition itself, antioxidants and any other 
ingredient customarily used in compositions intended for topical 
application. 
Especially preferred compositions are anhydrous gels, creams and fatty 
ointments or milks comprising, in addition to the compounds defined above, 
fatty alcohols, oxyethylenated or polyglycerolated fatty alcohols, fatty 
acid esters, natural or synthetic oils, waxes. 
In the treatment of skin aging, these compositions are more especially 
applied to areas exposed to light, on the basis of 1 to 10 mg cm.sup.2 of 
skin and for a period which can range from one week to 20 weeks or longer. 
The compositions according to the invention can also contain other active 
substances having an effect on skin aging, such as, more especially, 
retinoids such as, for example, all-trans-retinoic acid, 13-cis-retinoic 
acid, retinol, retinal and their derivatives. It is also possible to apply 
these derivatives in two stages, successively or separated by a period of 
time.