Use of salicylic acid and / or its derivatives and / or their salts to enhance or restore cutaneous tactile perception

Abstract

Use of salicylic acid and / or its derivatives and / or their salts, to increase or restore cutaneous tactile perception. The present invention relates to the cosmetic, non-therapeutic use of salicylic acid and / or its derivatives, and / or their salts, by topical application, to increase or restore cutaneous tactile perception, in particular to combat the decrease in cutaneous tactile perception due to age.

Description

Title of the invention: Use of salicylic acid and / or its derivatives and / or their salts, to enhance or restore cutaneous tactile perception

[0001] The present invention relates to the use of salicylic acid and / or its derivatives, and / or their salts, by topical application to the skin, to enhance or restore cutaneous tactile perception. Salicylic acid and its derivatives enable the development of neural extensions of human cutaneous sensory nerves.

[0002] The skin constitutes a major sensory organ, insofar as it is in direct contact with the external environment. It continuously receives a variety of thermal, mechanical or chemical stimuli.

[0003] Several types of sensory receptors have been identified in the skin. In addition to thermoreceptors, which transmit sensitivity to heat and cold, nociceptors, which are pain receptors, and pruriceptors, which are specific receptors for itching, various types of mechanical receptors have been identified. These latter receptors, which transmit sensitivity to pressure and vibration and fine epicritic or tactile sensitivity (which responds to light contact with the skin), consist of free nerve endings, Merkel discs located in the basal epidermis, Meissner corpuscles located in the papillary dermis, Pacinian corpuscles located in the deep dermis, and Ruffini corpuscles located in the dermis. Their density varies according to the region; thus, the palm of the hand is particularly well supplied, and the skin of the face also contains numerous receptors.

[0004] These mechanical receptors are innervated by sensory neurons called low-threshold mechanoreceptors (LTMRs), which respond to harmless mechanical stimuli. They are classified into different types based on the size of their cell bodies, the diameter of their axons, the degree of myelination, and the velocity of axonal conduction. The sensory neurons provide information to the central nervous system, which in turn generates an appropriate response. This makes it possible to recognize objects and discriminate textures, among other things.

[0005] These sensory neurons comprise a cell body from which neurites (axon and dendrites) emerge. The neurites are generally enveloped or in contact with the receptors mentioned above, in particular Merkel cells.

[0006] However, with age or in certain pathologies, particularly peripheral neuropathies due for example to diabetes (Diabetic Neuropathy, Mechanisms to Management, James L. Edwards, Andrea Vincent, Thomas Cheng, and Eva L. Feldman, The University of Michigan, Department of Neurology, Ann Arbor, Michigan 48109), chemotherapy, alcohol consumption, or neurodegenerative diseases all contribute to a decrease in tactile perception, or hypoesthesia. It is estimated that tactile deficits affect several hundred thousand people in France. However, their recognition remains marginal.

[0007] It is therefore understandable that it would be useful to have a means of restoring or increasing cutaneous tactile perception.

[0008] It has already been suggested that oral administration (EP 2 438 916; US 2002 / 040052) of certain plant extracts could lead to neurite elongation. However, this effect has only been exploited to treat certain neurodegenerative diseases or to improve learning, concentration, or memory skills.

[0009] In addition, WO2018002475 cites immortelle essential oil to increase or restore cutaneous tactile perception.

[0010] However, in view of the prior art, and therefore of the small number of active ingredients available in this field, there remains a need to identify other active compounds to increase or restore cutaneous tactile perception.

[0011] Thus, the present invention aims to propose other active ingredients to promote the elongation of neurites.

[0012] It also aims to offer other active ingredients to restore or increase cutaneous tactile perception, particularly during the application of a cosmetic product.

[0013] Surprisingly, the inventors discovered that treating sensory neurons with n-octanoyl-5-salicylic acid allows neurites to lengthen by releasing NGF growth factor and thus promotes increased cutaneous tactile perception.

[0014] It is known, particularly in diabetics, that NGF growth factor deficiency is a marker of decreased stimulation of sensory neurons (Role of Neurotrophins in Diabetic Neuropathy and Treatment with Nerve Growth Factors, DR Tomlinson, P. Fernyhough, and LT Diemel, Diabètes, Vol. 46 suppl. 2 September 1997), thus leading to a decrease in cutaneous tactile perception (in the case of sensory neurons innervating the skin).

[0015] In this context, the invention has as its primary object the cosmetic, non-therapeutic use of salicylic acid and / or its derivatives, and / or their salts, by topical application to the skin, to increase or restore cutaneous tactile perception, in particular to combat the decrease in cutaneous tactile perception due to age.

[0016] It also relates to a cosmetic, non-therapeutic process for increasing or restoring cutaneous tactile perception, in particular for combating the age-related decrease in cutaneous tactile perception, comprising topical application to the skin of a cosmetic composition, comprising at least salicylic acid and / or its derivatives, and / or their salts.

[0017] It also relates to salicylic acid and / or its derivatives, and / or their salts, or the composition comprising it or them for its topical use in a treatment aimed at increasing or restoring cutaneous tactile perception, by application to the skin of persons suffering from peripheral neuropathies, neurodegenerative diseases or destruction of nerve endings following a wound such as a burn.

[0018] Preferably, the skin concerned by the use and cosmetic treatment process described above is mature skin.

[0019] Preferably, the skins concerned by the use and cosmetic treatment process above are skins with reduced cutaneous tactile perception also called hypoesthesia.

[0020] Skin with diminished cutaneous tactile perception can be identified according to the method as described in Mechanisms of tactile sensory deterioration amongst the elderly, Lisa Skedung, Charles El Rawadi, Martin Arvidsson, Céline Farcet, Gustavo S Luengo, Lionel Breton, Mark W Rutland, Scientific Reports, nature research, 2018; 8: 5303. Definitions

[0021] By "skin" we mean the entire skin of the body, and the scalp and preferably the skin of the face, hands, décolletage, neck, arms and forearms, feet and even more preferably the skin of the face (in particular the forehead, nose, cheeks, chin, lips) and hands.

[0022] By "topical application" is meant an application to the surface of the skin in question.

[0023] The term “cosmetic composition” means a composition comprising a physiologically acceptable medium, that is to say, a medium compatible with the skin.

[0024] By "increasing cutaneous tactile perception", we mean here improving cutaneous tactile perception, in particular stimulating the elongation of neurites of human sensory neurons, in particular by stimulating NGF signaling.

[0025] By "restore cutaneous touch perception", we mean here restoring any alteration of cutaneous touch perception, in particular stimulating the elongation of neurites of human sensory neurons, in particular by stimulating NGF signaling.

[0026] By "mature skin" we mean here the skin of subjects aged at least 40 years, preferably at least 50 years, even better at least 70 years, even more preferably at least 80 years. Detailed description of the invention

[0027] Salicylic acid and its derivatives

[0028] The present invention relates to the cosmetic, non-therapeutic use of salicylic acid and / or its derivatives, and / or their salts, by topical application to the skin, to increase or restore cutaneous tactile perception, in particular to combat the decrease in cutaneous tactile perception due to age.

[0029] By "their salts" we mean salts derived from a mineral or organic base.

[0030] Preferably, the salicylic acid derivatives are in particular of the following formula (I):

[0031] [Chem.l] (I)

[0032] in which: - The radical Ra designates: an aliphatic chain having from 2 to 22 carbon atoms, saturated, linear, branched or cyclic; an unsaturated chain having from 2 to 22 carbon atoms containing one or more double bonds that may be conjugated; an aromatic ring linked to the carbonyl radical directly or via saturated or unsaturated aliphatic chains having from 2 to 7 carbon atoms; said groups may be substituted by one or more substituents, identical or different, chosen from: (a) halogen atoms, (b) the trifluoromethyl group, (c) hydroxyl groups in free form or esterified by an acid having from 1 to 6 carbon atoms, or (d) a carboxyl function in free form or esterified by a lower alcohol having from 1 to 6 carbon atoms; - Rb is a hydroxyl group; as well as their salts obtained by salification with a mineral or organic base.

[0033] According to one embodiment, the radical Ra designates: - a saturated, linear, branched, or cyclic aliphatic chain containing 3 to 11 carbon atoms; or - an unsaturated chain containing 3 to 17 carbon atoms and comprising one or several double bonds, conjugated or not; said hydrocarbon chains may be substituted by one or more substituents, identical or different, chosen from: (a) halogen atoms; (b) the trifluoromethyl group; (c) hydroxyl groups in free form or esterified by an acid having from 1 to 6 carbon atoms; or (d) a carboxyl function in free form or esterified by a lower alcohol having from 1 to 6 carbon atoms; as well as their salts obtained by salification with a mineral or organic base.

[0034] The compounds most particularly preferred are those in which the radical Ra is a C3-Cn alkyl group. Among the compounds of formula (I) particularly preferred, the following may be mentioned: n-octanoyl-5-salicylic acid (or capryloyl salicylic acid); n-decanoyl-5-salicylic acid; n-dodecanoyl-5-salicylic acid; n-heptyloxy-5-salicylic acid and their corresponding salts.

[0035] The salicylic acid compound is advantageously selected from salicylic acid and n-octanoyl-5-salicylic acid. N-octanoyl-5-salicylic acid is preferred. N-octanoyl-5-salicylic acid (or capryloyl salicylic acid) is offered under the name MEXORYL SAB® by NOVEAL.

[0036] Examples of mineral bases include alkali or alkaline-earth metal hydroxides such as sodium hydroxide, potassium hydroxide or ammonia.

[0037] Among the organic bases, amines and alkanolamines can be mentioned. Quaternary salts such as those described in French patent FR 2 607 498 are particularly interesting. The compounds of formula (I) usable according to the invention are described in US patents 6,159,479, US 5,558,871, FR 2,581,542, FR 2 607 498, US 4,767,750, EP 378,936, US 5,267,407, US 5,667,789, US 5,580,549, and EP A-570,230.

[0038] Preferably, salicylic acid and / or its derivatives and / or their salts as described above is / are present in the composition according to the invention in a concentration of 0.0001% to 20% by weight of active material, relative to the total weight of the composition, preferably in a concentration of 0.001% to 15% by weight of active material, even better in a concentration of 0.01% to 10% by weight of active material, even more preferably in a concentration of 0.1% to 5% by weight of active material, even more preferably in a concentration of 1% to 2% by weight of active material, relative to the total weight of the composition. Composition

[0039] The aforementioned properties can be exploited by using salicylic acid and / or its derivatives within a composition, preferably cosmetic, for topical use.

[0040] Salicylic acid and / or its derivatives and / or their salts, thus makes it possible to increase the tactile sensations felt by the subject on whom this care product is applied, during the application of the product, and in particular to better perceive its texture or its glide.

[0041] Salicylic acid and / or its derivatives and / or their salts, or the composition comprising it, can be applied to any part of the body and preferably to the skin of the face and / or hands, which are the most innervated areas.

[0042] In particular, it can be applied to the skin of subjects suffering from a loss of tactile sensation, in particular elderly subjects or those suffering from pathologies, including peripheral neuropathies, due in particular to diabetes or chemotherapy, neurodegenerative diseases, or destruction of nerve endings following a wound such as a burn.

[0043] By "elderly subject" is meant a subject aged at least 40 years, preferably at least 50 years, even better at least 70 years, even more preferably at least 80 years.

[0044] The compositions, particularly cosmetic ones, that may be used in the context of the invention generally include a physiologically acceptable medium.

[0045] By "physiologically acceptable medium" is understood a medium compatible with keratinous materials, and in particular the skin.

[0046] More particularly, said physiologically acceptable medium may comprise water and / or one or more water-miscible organic solvents which may be selected from linear or branched C1-C6 monoalcohols such as ethanol, isopropanol, tert-butanol; polyols such as glycerol, propylene glycol, hexylene glycol (or 2-methyl-2,4-pentanediol), and polyethylene glycols; polyol ethers such as dipropylene glycol monomethyl ether; and mixtures thereof.

[0047] Preferably, the composition according to the invention has a water content ranging from 20% to 95% by weight, even better from 40% to 90% by weight relative to the total weight of the composition.

[0048] Advantageously, the composition comprises one or more water-miscible organic solvents in a content ranging from 0.5% to 25% by weight, preferably from 5% to 20% by weight, even better from 10% to 15% by weight relative to the total weight of the composition.

[0049] The composition according to the invention may include water and / or all the additives usually employed in the intended field of application.

[0050] Examples include organic solvents distinct from the aforementioned water-miscible organic solvents, in particular C2-C10 carboxylic acid esters; carbonaceous and / or silicone oils of mineral, animal and / or vegetable origin; water, waxes, pigments, fillers, colorants, surfactants, emulsifiers, co-emulsifiers; cosmetic or dermatological actives, UV filters, polymers, hydrophilic or lipophilic gelling agents, thickeners, preservatives, perfumes, bactericides, odor absorbers, antioxidants.

[0051] These potential adjuvants may be present in the composition at a concentration of 0.001% to 80% by weight, preferably 0.01% to 40% by weight, and even better 0.1% to 20% relative to the total weight of the composition. These adjuvants, depending on their nature, may be introduced into the oil phase, the aqueous phase, and / or the lipid vesicles.

[0052] Of course, a person skilled in the art will take care to choose this or these possible complementary ingredients and / or active ingredients, and / or their quantity, in such a way that the advantageous properties of salicylic acid and / or its derivatives and / or their salts are not, or substantially not, altered by the envisaged addition.

[0053] The compositions according to the invention can be presented in all the pharmaceutical forms conventionally used for topical application, and in particular in the form of aqueous solutions, hydroalcoholic solutions, oil-in-water (O / W) or water-in-oil (W / O) or multiple (triple: W / O / W or W / O / O) emulsions, aqueous gels, or dispersions of an oily phase in an aqueous phase using spherules, these spherules being lipid vesicles of ionic and / or non-ionic type (liposomes, niosomes, oleosomes). These compositions are prepared according to conventional methods.

[0054] Advantageously, the compositions according to the invention are in the form of a gel, emulsion, powder, or paste. Furthermore, the composition according to the invention may be more or less fluid and have the appearance of a white or colored cream, ointment, milk, lotion, serum, paste, foaming gel, scrub, mask, treatment, toner, or mousse. It may optionally be applied to the skin in the form of an aerosol. It may also be in solid form, for example, in the form of a stick.

[0055] A composition according to the invention may include an oily phase.

[0056] By "liquid fats" is meant a compound having a melting point below about 30-35 °C such as oils, as opposed to solid fats, such as waxes, which have a melting point above about 50 °C.

[0057] Examples of oils that can be used in the composition of the invention include: - hydrocarbon oils of animal origin; - hydrocarbon oils of vegetable origin, - synthetic esters and ethers, particularly of fatty acids, such as oils with formulas R'COOR2 and R'OR2 in which R' represents the remainder of a fatty acid containing 8 to 29 carbon atoms, and R2 represents a hydrocarbon chain, branched or unbranched, containing 3 to 30 carbon atoms; - linear or branched hydrocarbons, of mineral or synthetic origin; - fatty alcohols having from 8 to 26 carbon atoms; - partially hydrocarbon and / or silicone-based fluorinated oils; - silicone oils; - their mixtures.

[0058] In the list of oils cited above, "hydrocarbon oil" means any oil consisting predominantly of carbon and hydrogen atoms, and possibly of ester, ether, fluorine, carboxylic acid, and / or alcohol groups. Other fatty substances that may be present in the oil phase include, for example, fatty acids containing 8 to 30 carbon atoms; waxes; silicone resins; and silicone elastomers. These fatty substances can be selected in a variety of ways by those skilled in the art to prepare a composition having the desired properties, for example, of consistency or texture.

[0059] According to a particular embodiment of the invention, the composition according to the invention is a water-in-oil (W / O) or oil-in-water (O / W) emulsion. The proportion of the oil phase of the emulsion can range from 5 to 90% by weight, and preferably from 5 to 60% by weight relative to the total weight of the composition. Emulsions generally contain at least one emulsifier selected from amphoteric, anionic, cationic, or nonionic emulsifiers, used alone or in mixtures, and optionally a co-emulsifier. The emulsifiers are chosen appropriately depending on the emulsion to be obtained (W / O or O / W). The emulsifier and the co-emulsifier are generally present in the composition in a proportion ranging from 0.3 to 30% by weight, and preferably from 0.5 to 20% by weight relative to the total weight of the composition.

[0060] For W / O emulsions, dimethicone copolyols and alkyl-dimethicone copolyols can be cited as examples of emulsifiers. A crosslinked solid organopolysiloxane elastomer comprising at least one oxyalkylated group can also be used as a surfactant in W / O emulsions.

[0061] For O / W emulsions, non-ionic emulsifiers can be cited as examples.

[0062] The compositions according to the invention may be applied directly to the skin or, alternatively, to occlusive or non-occlusive cosmetic carriers intended for localized application to the skin. Examples of such carriers, which are not limited to a patch, a wipe, a roll-on, and a pen, may be included. The composition may or may not be rinsed off after application to the skin.

[0063] Throughout the description, including the claims, the expression "at least one" shall be understood as synonymous with "one or more" unless otherwise stated. specified.

[0064] The expressions "more than", "between ... and ..." and "ranging from ... to ..." should be understood inclusive of limits, unless otherwise specified.

[0065] The following examples and figures are presented by way of illustration and not limitation of the invention. The compounds are, as appropriate, cited by chemical names or by CTFA (International Cosmetic Ingredient Dictionary and Handbook) names. Brief description of the drawings

[0066] [Fig-1]: Evaluation of the effects of the compound n-octanoyl-5-salicylic acid in the co-cultures of human sensory neurons / primary human keratinocytes: proliferation of neurites via NGF signaling.

[0067] [Fig.2]: Evaluation of the effects of the compound n-octanoyl-5-salicylic acid in the co-cultures of human sensory neurons / primary human keratinocytes: proliferation of neurites.

[0068] [Fig.3]: Evaluation of the effects of the compound n-octanoyl-5-salicylic acid in the co-cultures of human sensory neurons / primary human keratinocytes: NGF release Examples

[0069] Example - Evaluation of n-octanoyl-5-salicylic acid (C8-SA) on increasing tactile perception by lengthening sensory neuron neurites via the release of NGF growth factor

[0070] A) Materials and Methods

[0071] i) Generation of hiPS and differentiation of human sensory neurons in monolayer:

[0072] Primary skin fibroblasts were infected with a lentivirus encoded for KLF4, OCT4, SOX2, and c-MYC. HiPS colonies were harvested approximately 4 to 6 weeks post-infection, depending on their morphology, and propagated in mTESR1 medium in Petri dishes coated with BD Matrigel®. The HiPS cells were seeded into 6 well culture plates coated with a thin layer of BD Matrigel® and cultured at 37°C in DMEM-F12 medium supplemented with 0.1 pM retinoic acid, 1 pg / mL EPO, 10% KSR, 1% P / S, and an inhibitor cocktail for 10 days. On day 8, the cells were seeded, 17,000 cells per well, onto a 96-well plate coated with a thin layer of BD Matrigel®. On day 10, the medium was replaced with DMEM-F12 supplemented with 10 ng / mL of NT-3, 10 ng / mL of GDNF, 10 ng / mL of BDNF, 10 ng / mL of NGF, and 1% P / S. The medium was changed every 2 or 3 days.

[0073] ii) Immunostaining and analyzes

[0074] The cells were fixed with a 2% paraformaldehyde solution in the medium Cell culture was performed. Cells were permeabilized, and nonspecific sites were blocked with PBS containing 0.1% saponin and 1% fetal bovine serum. Human sensory neurons were stained with primary antibodies (β-tubulin Sigma; T8660) for 2 hours. These antibodies were detected with secondary antibodies (Alexa Fluor, Invitrogen) for 1 hour. Nuclei were labeled with Hoechst's solution. Images were acquired using InCell Analyzer™ 2000 (GE Healthcare).

[0075] ii.l) Evaluation of the effects of the compound n-octanoyl-5-salicylic acid in co-cultures of human sensory neurons / human primary keratinocytes: neurite proliferation via NGF signaling

[0076] hiPS cells were seeded in 96-well plates coated with Matrigel® in M1 C-28055 culture medium from Promocell. After 7 days in culture, keratinocytes derived from a 38-year-old donor were added to the neurons, and the culture medium was changed to a mixture of M2 C-28056 from Promocell and a keratinocyte culture medium. After 24 hours of incubation, the culture medium was changed to a growth factor-free medium containing n-octanoyl-5-salicylic acid at a concentration relative to the vehicle (final concentration of 0.1% DMSO) with or without NGF-blocking antibodies (abcam, ab6199) (6 wells per condition). After 4 days of incubation, the cells were analyzed by α3-tubulin immunofluorescence to assess neurite length.

[0077] ii.2) Evaluation of the effects of the compound n-octanoyl-5-salicylic acid in the co Human sensory neuron cultures / primary human keratinocytes: NGF release

[0078] hiPS were seeded in 96-well plates coated with Matrigel® in M1 C-28055 culture medium from Promocell. After 7 days in culture, keratinocytes derived from a 38-year-old donor were added to the neurons, and the culture medium was changed to a mixture of M2 C-28056 from Promocell and a keratinocyte culture medium. After 24 hours of incubation, the culture medium was replaced with a growth factor-free medium, in the presence of the compound at a concentration relative to the vehicle (final concentration of 0.1% DMSO; 6 wells per condition). After 4 days of incubation, NGF release was analyzed in the supernatants by ELISA assay following the supplier's instructions (Biotechne; DY256) and the cells were analyzed with immunofluorescence [3-tubulin to assess neurite length.

[0079] B) Results

[0080] i) Evaluation of the effects of the compound n-octanoyl-5-salicylic acid in the co Human sensory neuron cultures / primary human keratinocytes: neurite proliferation via NGF signaling (see [Fig.1])

[0081] n-Octanoyl-5-salicylic acid induces neurite growth in human sensory neurons via the NGF pathway. The assays were performed as described in the methods. n-Octanoyl-5-salicylic acid was applied to cultures of human sensory neurons in the presence or absence of anti-NGF antibodies for 4 days. NGF 50 ng / mL was used as a positive control for neurite growth induction. The cultures were stained for [3-III-tubulin (green)] and with 4',6-diamidino-2-phenylindole (DAPI; blue).

[0082] Images were acquired at 20x magnification. Neuron neurite lengths were normalized by the number of neurons and expressed as a percentage of the control (vehicle). Analysis of variance (ANOVA) followed by Dunnett's test was performed. **p < 0.01 vs. control. *p < 0.05 vs. C8-SA + anti-NGF. **p < 0.01 vs. C8-SA + anti-NGF.

[0083] The results are presented in [Fig.1] and in Table 1 below.

[0084] [Tables 1] Neurite length (normalized by the number of sensory neurons) Sum of 20 images Mean % of control Mean Standard deviation P (T-test) Control DMSO 921 1065 86.5 100 4 1127 105.8 1145 107.6 1041 97.8 1172 110.1 982 92.3 C8-SA IpM 1333 1321 125.2 124 4 0.001 1211 113.8 1299 122.0 1215 114.1 1381 129.7 1490 139.9

[0085] An increase in the length of the neurites of sensory neurons is observed humans at IpM of n-octanoyl-5-salicylic acid (C8-SA) and that the use of anti-NGF antibodies inhibits this effect, thus showing the involvement of the NGF pathway.

[0086] ii.2) Evaluation of the effects of the compound n-octanoyl-5-salicylic acid in the co Human sensory neuron cultures / primary human keratinocytes: NGF release (see Figures 2 and 3)

[0087] n-Octanoyl-5-salicylic acid induces the growth of human sensory neuron neurites by releasing NGF. The tests were performed as described in the methods. n-Octanoyl-5-salicylic acid was applied to cultures of human sensory neurons for 4 days. The length of the neurites and the release of NGF were measured. The cultures were stained for [3-III-tubulin (red)] and with 4',6-diamidino-2-phenylindole (DAPI; blue).

[0088] Images were taken at 20x magnification. The neurite length of the neurons was normalized by the number of neurons and expressed as a percentage of the control (vehicle) and analyzed using an analysis of variance (ANOVA) followed by Dunnett's test or Student's t-test. *p < 0.05 vs control, p < 0.001 vs control.

[0089] The results are presented in Figures 2 and 3 and in Tables 2 and 3 below.

[0090] [Tables2] Length of extensions per human sensory neuron Sum of 20 images Mean % of control Mean Standard deviation Control DMSO 687 637 108 100 5 640 100 655 103 493 78 685 108 659 103 Anti-NGF 1 / 100 664 628 104 99 3 663 104 644 101 603 95 641 101 554 87 C8-SA IpM 649 791 102 124 6 791 124 765 120 886 139 897 141 760 119 C8-SA IpM + anti-NGF 1 / 100 631 668 99 105 4 715 112 681 107 738 116 592 93 648 102 NGF 50 ng / ml 763 793 120 125 3 879 138 778 122 758 119 788 124 792 124 NGF 50 ng / ml + anti-NGF 1 / 100 629 649 99 102 5 526 83 686 108,687 108,749 118,618 97

[0091] [Tables3] OMSO C8-SA IgM Control 82.55 P Lu N 102.24 117.90 100.62 112.23 94.33 116.47 88.51 103.58 89.51 125.04 Mean 93.0 117.3 Standard Deviation 3.1 3.6

[0092] Fig. 2 shows an increase in the length of the neurites of sensory neurons at IqM of n-octanoyl-5-salicylic acid (C8-SA).

[0093] Fig. 3 shows an increase in the release of growth factor NGF at IqM of n-octanoyl-5-salicylic acid (C8-SA).

Claims

Demands

1.

2. Salicylic acid and / or its derivatives, and / or their salts, or composition comprising it or them for use by topical application to the skin, in a treatment aimed at increasing or restoring cutaneous tactile perception, in particular aimed at combating the decline in cutaneous tactile perception due to age. Salicylic acid and / or its derivatives, and / or their salts, or a composition comprising it or them according to claim 1, characterized in that said salicylic acid derivatives have the following formula (I):

3. in which: - The radical Ra designates: an aliphatic chain having from 2 to 22 carbon atoms, saturated, linear, branched or cyclic; an unsaturated chain having from 2 to 22 carbon atoms containing one or more double bonds that may be conjugated; an aromatic ring linked to the carbonyl radical directly or via saturated or unsaturated aliphatic chains having from 2 to 7 carbon atoms; said groups may be substituted by one or more substituents, identical or different, chosen from: (a) halogen atoms, (b) the trifluoromethyl group, (c) hydroxyl groups in free form or esterified by an acid having from 1 to 6 carbon atoms, or (d) a carboxyl function in free form or esterified by a lower alcohol having from 1 to 6 carbon atoms; - Rb is a hydroxyl group; as well as salts derived from a mineral or organic base of said derivatives of formula (I). Salicylic acid and / or its derivatives, and / or their salts, or a composition comprising it or them according to claim 1 or 2, characterized in that said salicylic acid and / or its derivatives, and / or their salts, is applied to the skin of the face and / or hands.

4. Salicylic acid and / or its derivatives, and / or their salts, or a composition comprising it or them according to any one of the preceding claims, characterized in that said salicylic acid and / or its derivatives, and / or their salts, is applied to mature skin, preferably to the skin of a subject aged at least 40 years.

5. Salicylic acid and / or its derivatives, and / or their salts, or a composition comprising it or them according to any one of the preceding claims, characterized in that said salicylic acid and / or its derivatives, and / or their salts, is applied to skin exhibiting diminished cutaneous tactile perception.

6. Salicylic acid and / or its derivatives, and / or their salts, or a composition comprising it or them according to any one of the preceding claims, characterized in that said salicylic acid and / or its derivatives, and / or their salts, is selected from salicylic acid, n-octanoyl-5-salicylic acid, and mixtures thereof.

7. Composition according to any one of claims 1 to 6 wherein said salicylic acid and / or its derivatives, and / or their salts are present in said composition in a concentration of 0.0001% to 20% by weight of active material, relative to the total weight of the composition, preferably in a concentration of 0.001% to 15% by weight of active material, even better in a concentration of 0.01% to 10% by weight of active material, even more preferably in a concentration of 0.1% to 5% by weight of active material, even more preferably in a concentration of 1% to 2% by weight of active material, relative to the total weight of the composition.

8. Salicylic acid and / or its derivatives, and / or their salts, or composition comprising it or them for use in a treatment intended to increase or restore cutaneous tactile perception, by application to the skin of persons suffering from peripheral neuropathies, neurodegenerative diseases or destruction of nerve endings following an injury such as a burn.

Images