Electroporation process for delivering a composition comprising at least one peptide with a molecular weight ranging from 500 Da to 20 kDa

Abstract

Electroporation method for delivering a composition comprising at least one peptide with a molecular weight ranging from 500 Da to 20 kDa. The present invention relates to an electroporation method for delivering a composition through human keratinous materials, the composition comprising a peptide with a molecular weight ranging from 500 Da to 20 kDa. The electroporation method comprises exposing the composition in contact with said keratinous materials to a succession of pulses of an electric current. The electric current is supplied by an electroporation device having an electrode (2) and a counter electrode (3). Each pulse has a duration of between 1 ms and 5 s with a rest interval between them of between 0.1 and 5 s, and the electric current has a voltage amplitude of between 20 and 400 V and an intensity of between 0.1 and 10 mA. Figure for the abstract: Figure 1

Description

Title of the invention: Electroporation process for delivering a composition comprising at least one peptide with a molecular weight ranging from 500 Da to 20 kDa technical field

[0001] The present invention relates to the field of care of keratinous materials, in particular of the skin.

[0002] For the purposes of this invention, "keratinous materials" means, in particular, skin, lips and / or eyelashes, especially skin and / or lips, and preferably skin of the body and / or face, and more preferably of the face.

[0003] Nowadays, there are numerous treatments, both cosmetic and non-cosmetic, that can enhance the appearance of human beings. These treatments, hereafter referred to as aesthetic treatments, can act in many ways, and for example, consist of making certain skin imperfections disappear or masking them, or even reducing or eliminating the signs of aging.

[0004] Skin aging results from the effects of intrinsic and extrinsic factors on the skin. During the aging process, alterations in skin structure and function occur. The main clinical signs resulting from these changes in skin metabolism are the appearance of wrinkles and fine lines due to sagging and loss of tissue elasticity.

[0005] Furthermore, intrinsic aging, which induces changes in the skin, notably causes a slowing of the renewal of skin cells, which essentially results in the appearance of clinical alterations such as the reduction of subcutaneous adipose tissue and the appearance of fine wrinkles or lines, and in histopathological changes such as an increase in the number and thickness of elastic fibers, a loss of vertical fibers of the membrane of the elastic tissue, and the presence of large irregular fibroblasts in the cells of this elastic tissue. Previous technique

[0006] It is known to introduce active ingredients into cosmetic and / or dermatological compositions in order to beautify the appearance of the skin, and in particular to combat the signs of aging.

[0007] For example, there has long been research into formulating peptides, and in particular N-acylamino-amide elastase inhibitor compounds, in the cosmetic and dermatological fields, in various galenic forms, due to its numerous beneficial properties.

[0008] In particular, N-acetyl-3-trifluoromethyl-phenyl-(valine-glycine) is a small peptide derivative that exhibits numerous advantageous properties, and which can notably act as an anti-aging active ingredient. This peptide helps to increase epidermal regeneration and maintain epidermal homeostasis.

[0009] Thus, due to their properties, these peptides are effective in combating the signs of skin aging, for example in improving the radiance of the complexion and reducing fine lines and / or wrinkles of the skin.

[0010] Unfortunately, current formulations do not allow these active ingredients to penetrate effectively into keratinous materials, and in particular into the skin.

[0011] Furthermore, it is known that applying an electric current to the skin can promote the penetration of an active ingredient. It is thus known to treat human keratinous materials using electroporation devices. Electroporation allows the diffusion of active ingredients through the skin by means of electrical stimulation in a non-invasive manner.

[0012] Electroporation makes the skin surface permeabilized, allowing the active ingredients to pass through by diffusion, or even by electrophoresis when they are charged.

[0013] Applications US 2010 / 255079, US 2012 / 065575, US 2013 / 345307, US 2013 / 345661, WO 2010 / 112708 or WO 2008 / 045272 describe devices that combine electric current with cosmetic actives.

[0014] It is also known, for example, in EP 2 408 801, to use iontophoresis to deliver tetrapeptide elastase inhibitors. Furthermore, WO 2010 / 118880 describes the transdermal application of tripeptides.

[0015] Nevertheless, these methods remain, on the one hand, ineffective, particularly for increasing the performance of formulas comprising peptides, and in particular N-acylamino-amide compounds that inhibit elastases, and on the other hand, present risks of skin damage. Description of the invention

[0016] There therefore remains a need to further perfect the processes which promote the penetration of active ingredients through keratinous materials in order to increase the efficiency of electroporation, and to benefit from a treatment process, in particular cosmetic or dermatological, of keratinous materials, making it possible to increase the performance and accelerate the action of formulas containing peptides with molecular weights ranging from 500 Da to 20 kDa, and in particular N-acylamino-amide compounds that inhibit elastases, in particular N-acetyl-3-trifluoromethyl-phenyl-(valine-glycine), by increasing the supply of active ingredients inside the living part of keratinous materials, while being able to be used comfortably and safely.

[0017] There is particular interest in cosmetic treatments at home that are practically as effective and powerful as cosmetic treatments performed by professionals, in order to target deeper levels of the dermis at home and to treat in particular moderate to severe wrinkles, sun damage and pigmentation, and which provide results that become apparent immediately or shortly after a single treatment, painlessly and without muscle contraction induced by electroporation.

[0018] There is a need to increase the cutaneous release of active ingredients in a targeted manner within the living parts of keratinous materials, and their bioavailability, in order to have effective cosmetic treatments at home.

[0019] The invention aims to meet all or part of these needs. Summary of the invention

[0020] Thus, according to a first aspect thereof, the present invention relates to an electroporation process for delivering a composition through human keratinous materials, the composition comprising at least one peptide with a molecular weight ranging from 500 Da to 20 kDa, and in particular at least one N-acylamino-amide compound inhibiting elastases, the electroporation process comprising exposing the composition in contact with said keratinous materials to a succession of pulses of an electric current, the electric current being supplied by an electroporation device having at least one electrode and at least one counter-electrode, each pulse having a duration (tpUke) of between 1 ms and 5 s, preferably between 5 ms and 3 s, even better between 10 ms and 2 s, with a rest interval (Toff) between them of between 0.1 s and 5 s, preferably between 0.3 s and 3 s, even better Ideally, between 0.5 seconds and 2 seconds.and the electric current having a voltage range from 20 V to 400 V, better from 25 V to 300 V, even better from 30 V to 200 V, and an intensity ranging from 0.1 mA to 10 mA, better from 0.2 mA to 2 mA, even better from 0.25 mA to 1 mA.

[0021] The process according to the invention is non-therapeutic and for exclusively cosmetic purposes.

[0022] By "rest interval", it is necessary to understand the pulse-free duration that separates two consecutive pulses; preferably, during this interval, no voltage is applied by the electroporation device to the keratinous materials.

[0023] The number N of consecutive pulses applied can be between 2 and 15000, better between 10 and 5000, even better between 50 and 500. These N successive pulses are referred to in the following as a “pulse train”.

[0024] Preferably, the polarity of the applied voltage is constant, being chosen according to that of the compound or compounds whose diffusion in keratinous materials is to be improved.

[0025] The method according to the invention makes it possible to carry out cosmetic treatments at home that are much more effective than conventional cosmetic treatments at home, with results that become apparent immediately or shortly after a single treatment.

[0026] Indeed, the cutaneous release of peptides with molecular weights ranging from 500 Da to 20 kDa, and in particular of N-acylamino-amide elastase inhibitor compounds, inside the living parts of keratinous materials, as well as their bioavailability, are increased, compared to classic home cosmetic treatments, in a painless manner, without muscle contraction induced by electroporation and without alteration of keratinous materials, and in particular of the skin.

[0027] In particular, the process according to the invention allows changes in skin impedances and therefore an increase in the permeability of peptides with molecular weights ranging from 500 Da to 20 kDa, and in particular of N-acylamino-amide elastase inhibitor compounds, through keratinous materials, and in particular through the skin.

[0028] Thus, the diffusion of peptides with molecular weights ranging from 500 Da to 20 kDa, and in particular of N-acylamino-amide elastase inhibitor compounds, through keratinous materials, and in particular through the skin, is increased by the application of the process according to the invention.

[0029] According to a preferred embodiment, the method includes a topical application of the composition to the area to be treated before the application of the electric current and / or during said application. Detailed description Electroporation device

[0030] According to the invention, the electric current is supplied by an electroporation device having at least one electrode and at least one counter electrode.

[0031] According to the invention, the pulses preferably have a voltage amplitude ranging from 30 V to 200 V and an intensity ranging from 0.25 mA to 1 mA. The amplitude is measured peak-to-peak and the intensity is the instantaneous intensity.

[0032] The maximum current density per pulse can be less than or equal to 0.5 mA / cm2.

[0033] Preferably, the electric current has a direct polarity (DC current), the polarity of the electrode being, for example, negative or positive with respect to that of the counter electrode, depending on the polarity of the applied compounds. Preferably, the polarity of the electrode is negative with respect to that of the counter electrode.

[0034] The pulses may have a constant maximum amplitude. The pulses may have a variable amplitude from one pulse to the next, for example, which increases from a minimum amplitude, reaches the maximum amplitude, then possibly decreases towards the minimum amplitude.

[0035] It is possible to combine two or more pulse waveforms simultaneously or alternately. The application of the current may include the generation of a current having sinusoidal waveforms, non-sinusoidal waveforms, periodic square waveforms, rectangular waveforms, sawtooth waveforms, peaked waveforms, bell waveforms, trapezoidal waveforms, triangular waveforms or combinations thereof.

[0036] Preferably, the electric current has a square or rectangular waveform. A pulse can thus have a voltage square wave shape.

[0037] According to a preferred embodiment, the applied current has a duty cycle (tpUke / (tpuiSe+TOff)) varying from 10% to 90%, preferably from 20% to 80%, where tpUke denotes the duration of a pulse and Toff the interval between two successive pulses.

[0038] Preferably, the maximum voltage between the electrode and the counter electrode in open circuit is from 150 V to 250 V. Electrodes

[0039] According to a preferred embodiment, the process includes the step of manually moving the electrode(s) of the electroporation device over the keratinous materials while subjecting the latter to said electric current pulses.

[0040] According to another embodiment, the active electrode is stationary and applied to a single location on the keratinous materials, for example through an adhesive.

[0041] The electrode(s) may have a rounded surface for contact with keratinous materials.

[0042] Preferably, the surface area of ​​the electrode(s) in contact with the keratinous materials varies from 2 cm² to 20 cm². The current density, for example, ranges from 0.1 mA / cm² to 0.5 mA / cm². Preferably, the counter electrode is static and has a surface area in contact with the human keratinous materials greater than that of the electrode, which is displaced in contact with the keratinous materials, the surface area of ​​the counter electrode preferably being greater than 1.5 times that of the electrode.

[0043] The electroporation device may include at least one reservoir containing an effective quantity of a composition according to the invention.

[0044] In particular, the device may include at least one electrode and one or more compositions stored in a reservoir such as a cavity, a gel, a laminate, a membrane, a porous structure, a matrix or a substrate.

[0045] More specifically, the device may include at least one active electrode electrically coupled to a reservoir containing a cosmetic composition according to the invention.

[0046] The reservoir may comprise any shape or material used to retain a composition according to the invention.

[0047] The reservoir may include one or more ion exchange membranes, semi-permeable membranes, or porous membranes or gels capable of retaining at least temporarily a composition according to the invention.

[0048] The reservoir may include one or more cavities formed by a structure.

[0049] In particular, the electroporation device may include one or more ion exchange membranes which can be positioned to serve as a polarity-selective barrier between the composition reservoir according to the invention and a biological interface.

[0050] The reservoir may be a hollow cavity at the end of the electrode. Alternatively, according to a particular embodiment, the reservoir is an absorbent material for containing the composition according to the invention.

[0051] The reservoir can, in particular, be connected to a piston or any other means of dispensing the composition. Thus, the active electrode can be equipped with a type of ball applicator fed by a piston. The piston can be actuated during the use of the electroporation device.

[0052] The electroporation device may also be an electroporation patch or an electroporation face mask.

[0053] Preferably, the electroporation device is held by hand. User interface

[0054] The electroporation device may include a user interface.

[0055] The user interface may be intended for data input regarding the types of waveforms to be applied as electrical stimuli. The user interface may include an alphanumeric keypad and a display. The alphanumeric keypad may be implemented as a touchscreen.

[0056] The user interface may in particular include directional arrow buttons and an input button for entering data into memory.

[0057] Waveform parameters can be entered using text boxes and / or drop-down menus. Regardless of the method of data entry, the user interface can provide a variety of prompts for the user to enter information.

[0058] The user interface may prompt the user to enter the duration of the treatment.

[0059] The user interface may prompt the user to enter the processing area.

[0060] The device may include a controller that executes logic routines to direct the user interface in order to present the user with the appropriate prompts. The controller then uses the entered parameters to generate, via its electronics, y including, but not limited to, the appropriate voltage based on the parameters entered by the user. Other sensors

[0061] According to a particular embodiment of the electroporation process, the process includes a step of measuring the skin temperature, the skin impedance and the pH of the composition.

[0062] Thus, the electroporation device may include at least a temperature sensor, an impedance sensor and / or a pH sensor.

[0063] The application of the current profile can thus be reduced to a safety level when a value measured by one of the sensors exceeds a range or a safety value.

[0064] According to a particular embodiment of the electroporation process, the process includes a step for measuring the pH of the composition. When the measured pH exceeds a pH safety range, the application of the current profile is switched to a safety level, for example, a safety level below 1 V, such as 0.5 V. The pH safety range is, for example, pH 4 to 7. In some embodiments, when the measured pH exceeds a pH safety range, for example, the range of 4 to 7, the device switches polarity for a short period to allow the pH to be rebalanced.

[0065] According to a particular embodiment of the electroporation process, the process includes a step of measuring skin impedance. When the measured impedance exceeds a safety impedance range, the application of the current profile is reduced to a safety level to prevent an undesired event. The safety level may be less than 1 V, such as 0.5 V. The safety impedance range may be from 5 kQ to 2 MQ.

[0066] According to a particular embodiment of the electroporation process, the process includes a step for measuring skin temperature. When the measured temperature exceeds a safety temperature value, the application of the current profile is switched to a safety level, for example below 1 V, such as 0.5 V. The safety temperature value can be chosen to be below 43 °C.

[0067] In a preferred embodiment of the electroporation process, the process comprises the steps of: - measurement of skin temperature, - measurement of the composition's impedance, and - pH measurement of the composition.

[0068] The device is configured to process the results and regulate the microcurrent and polarity. Process

[0069] The process according to the invention can be cosmetic and non-therapeutic.

[0070] According to a particular embodiment of the electroporation process, the process comprises the transdermal delivery of a composition according to the invention, comprising one or more peptides with molecular weights ranging from 500 Da to 20 kDa, and in particular one or more N-acylamino-amide compounds that inhibit elastases.

[0071] According to a particular embodiment of the invention, the method for delivering the composition according to the invention comprising at least one peptide with a molecular weight ranging from 500 Da to 20 kDa, in particular at least one N-acylaminoamide compound inhibiting elastases, in particular N-acetyl-3-trifluoromethyl-phenyl-(valine-glycine), through keratinous materials, comprises the application of a specific electrical current profile, from an electroporation device having at least one electrode and at least one counter electrode, for a specific duration sufficient to deliver transdermally the peptide(s) with a molecular weight ranging from 500 Da to 20 kDa, in particular the N-acylaminoamide compound(s) inhibiting elastases, in particular N-acetyl-3-trifluoromethyl-phenyl-(valine-glycine), to a biological subject.

[0072] Thus, the diffusion through human keratinous materials of peptide(s) with a molecular weight ranging from 500 Da to 20 kDa, in particular of the N-acylamino-amide elastase inhibitor(s), especially N-acetyl-3-trifluoromethyl-phenyl-(valine-glycine), can be increased by applying the electroporation process according to the invention. Such an increase in the diffusion of the active ingredient makes it possible to optimize the amount of active ingredient required for targeted treatments in the different layers of keratinous materials.

[0073] Electroporation treatment can be applied for a duration of 60 s to 1000 s.

[0074] In particular, the electroporation treatment is applied for a duration of 120 s to 480 s. Kit

[0075] According to a particular embodiment, the invention also provides an electroporation kit comprising: - an electroporation composition comprising at least one peptide with a molecular weight ranging from 500 Da to 20 kDa, including at least one N-acylamino-amide compound that inhibits elastases, in particular N-acetyl-3-trifluoromethyl-phenyl-(valine-glycine), and - an electroporation device for implementing the electroporation process as described above.

[0076] The present invention also proposes an electroporation kit comprising: - an electroporation composition comprising at least one peptide with a molecular weight ranging from 500 Da to 20 kDa, including at least one N-acylamino-amide compound that inhibits elastases, in particular N-acetyl-3-trifluoromethyl-phenyl-(valine-glycine), and - an electroporation device for delivering the electroporation composition through keratinous materials, configured to apply a negative current profile.

[0077] Preferably, the present invention provides a kit for implementing the process according to the invention, comprising: - an electroporation device having at least one electrode (2) and at least one counter electrode (3) and arranged to subject the keratinous materials to a succession of pulses of an electric current, each pulse having a duration (tpUke) of between 1 ms and 5 s, preferably between 5 ms and 3 s, preferably between 10 ms and 2 s, with a rest interval (Toff) between them of between 0.1 s and 5 s, preferably between 0.3 s and 3 s, preferably between 0.5 s and 2 s, and the electric current having a voltage amplitude of between 20 V and 400 V, preferably between 25 V and 300 V, preferably between 30 V and 200 V, and an intensity of between 0.1 mA and 10 mA, preferably between 0.2 mA and 2 mA, preferably between 0.25 mM at 1 mA, and - a composition comprising at least one peptide with a molecular weight ranging from 500 Da to 20 kDa, in particular at least one N-acylamino-amide elastase inhibitor compound, in particular at least N-acetyl-3-trifluoromethyl-phenyl-(valine-glycine).

[0078] The electroporation device and the composition can be packaged together, for example in the same package. Applications

[0079] In a preferred embodiment, the method, composition, and kit according to the invention make it possible to treat wrinkles and signs of aging, improve skin smoothness, quality, and appearance. It can thus be used to hydrate the skin, improve skin elasticity, enhance and / or reduce skin microrelief, and combat the signs of skin aging.

[0080] The method, composition, and kit according to the invention are particularly effective in delivering anti-aging ingredients that penetrate the skin beyond superficial levels, which can contribute to such effects. After ablative laser procedures or chemical peels, for example, electroporation can also improve the healing process by achieving a higher delivery of active ingredients. The rapid penetration that reaches a greater depth makes electroporation also effective for acne scars.

[0081] According to another particular embodiment, the process is used to minimize the effects of age on the skin, and / or pigmentation, and / or volume, and / or sagging of wrinkles, and / or tone and / or spots, and / or to improve the firmness, and / or radiance, and / or smoothness of the skin. Description of the figures

[0082] Other features, variations and advantages of the invention will become apparent from reading the description, non-limiting examples of its implementation, and from examining the accompanying drawings, in which: Figures

[0083] [Fig-1] [Fig.1] schematically represents an example of a device electroporation according to the invention,

[0084] [Fig.2] [Fig.2] is a block diagram of the device,

[0085] [Fig.3] [Fig.3] illustrates an example of an applied voltage waveform,

[0086] [Fig.4] [Fig.4] is a diagram comparing the delivery in kerato- topical delivery of N-acetyl-3-trifluoromethyl-phenyl-(valine-glycine) from a 1% simplex formula of N-acetyl-3-trifluoromethyl-phenyl-(valine-glycine), and delivery of N-acetyl-3-trifluoromethyl-phenyl-(valine-glycine) from a 1% simplex formula of N-acetyl-3-trifluoromethyl-phenyl-(valine-glycine) by electroporation, and

[0087] [Fig. 5] [Fig. 5] represents the amount of EGF that has penetrated the skin by a Elisa's technique.

[0088] Figure 1 shows an example of a treatment device 1 according to the invention.

[0089] This device 1 comprises at least two electrical outputs between which an electrical signal is generated.

[0090] In the example considered, the device 1 comprises at least one electrode 2, to be moved on the skin in the areas to be treated, and a counter electrode 3 to be fixed on the body, for example using a bracelet or an adhesive patch.

[0091] The electrode 2 can be carried, as illustrated in [Fig.1], by a housing 4 which houses an electronic signal generation circuit, or in a variant, not illustrated, carried by a handpiece which is connected by a cable to a static housing housing the electronic signal generation circuit.

[0092] The electronic signal generation circuit may include, as illustrated in [Fig.2], a central unit 11 with a microcontroller, for example of the ATMEGA type, which executes software to generate a signal of the desired shape, which is amplified by an amplifier 12 connected to the electrode 2 and the counter electrode 3.

[0093] The central unit 11 also manages the user interface 13, which includes by example a display 14 and one or more control buttons 15.

[0094] The electronic circuit can be powered by a battery 16 housed in the casing 4, or alternatively by a mains adapter.

[0095] The output signal can be modulated.

[0096] The output signal can be a periodic signal, with a given elementary pattern, which is modulated. For example, as illustrated in [Fig.3], the applied voltage is periodic, with N square-shaped pulses emitted, each with a duration tpUke of 10 ms for example, separated by pulse-free rest periods of duration Toff equal to 500 ms for example.

[0097] A duration tpuke less than or equal to 10 ms can reduce the risk of skin irritation or sensation of pain or induction of muscle contractions, knowing that the nature of the applied field, in particular the geometry of the electrodes and their configuration (very close or very far apart, superficial electric field versus through when the electrodes are far apart), can lead to different perception thresholds.

[0098] A rest period Toff greater than or equal to 100 ms allows the skin to recover a basal membrane potential between the application of the impulses.

[0099] The device 1 can be configured to generate an electrical signal between the electrode and the counter electrode, for a predefined number of pulses or pulse trains, for example by means of a pulse counter, or for a predefined duration, by means of a timer.

[0100] Electrode 2 preferably has a rounded shape.

[0101] The contact area with the skin of electrode 2 goes for example from 2 cm2 to 20 cm2.

[0102] The electric current density applied by electrode 2 goes, for example, from 0.1 mA / cm2 to 0.5 mA / cm2.

[0103] The voltage between electrode 2 and counter electrode 3 increases preferably when a resistive load is connected to them and the resistance of the load increases. The amplitude is, for example, practically zero for zero resistance up to a resistance of 10 kOhms, then increases until it reaches approximately 200 V in an open circuit.

[0104] The current (RMS) delivered by the device is preferably between 150 mA and 500 mA when it supplies a resistance whose value varies between 1 kOhm and 500 kOhms.

[0105] The device can be offered to the user with a composition P according to the invention to be applied to the skin, within a common packaging, such as a box for example.

[0106] The composition P according to the invention can be contained in any type of container, for example a container equipped with an applicator for applying the composition to the skin, or a pump bottle, among other possibilities.

[0107] Preferably, the applied voltage is unipolar, the voltage of electrode 2 being for example either always positive or always negative, depending on the nature of the active ingredient(s) contained in the composition. Composition

[0108] An electroporation composition for its use in an electroporation method as mentioned above is described.

[0109] A composition according to the invention has a viscosity such that the composition coats both the treated surface and the treatment electrode of the device, allowing a smooth and frictionless movement.

[0110] A composition according to the invention preferably has a viscosity between 0.001 Pa.s and 0.5 Pa.s, better between 0.005 Pa.s and 0.1 Pa.s, and even better between 0.01 Pa.s and 0.05 Pa.s.

[0111] The viscosity of the composition is measured at room temperature (25 °C) using an RM 200 Plus rheometer (LamyRheology).

[0112] According to a first preferred embodiment, a composition according to the invention is of the gel type, in particular of the aqueous gel type.

[0113] According to another preferred embodiment, a composition according to the invention is an emulsion, in particular a water-in-oil or oil-in-water emulsion, and preferably an oil-in-water emulsion, also known as a direct emulsion.

[0114] Preferably, a composition according to the invention is of the gel type, or is an oil-in-water emulsion.

[0115] Thus, a composition according to the invention may comprise an aqueous phase and / or an oily phase.

[0116] In some embodiments of the electroporation composition, the composition has a pH ranging from 2 to 7.5, preferably from 3 to 6, and more preferably from 3 to 5.

[0117] In some embodiments, when the measured pH exceeds a pH safety range, for example the range of 4 to 6, the device switches the polarity for a short period to allow the pH to be rebalanced.

[0118] As mentioned above, the electroporation method according to the present invention includes a step of applying to the skin a composition comprising a peptide with a molecular weight ranging from 500 Da to 20 kDa, in particular an N-acylamino-amide compound exhibiting elastase activity-inhibiting activity.

[0119] Peptides with molecular weights ranging from 500 Da to 20 kDa

[0120] Peptides are polymers of amino acids linked by peptide bonds.

[0121] According to the invention, the peptides used in the composition have a molecular weight ranging from 500 Da to 20 kDa.

[0122] According to the invention, the molecular weight can for example be measured by mass spectrometry or by gel chromatography filtration.

[0123] According to a preferred embodiment of the invention, the peptides have a molecular weight ranging from 100 Da to 50 kDa, and more preferably from 500 Da to 20 kDa.

[0124] The peptides of the invention can be modified by acylation on their N-terminal function and / or by esterification on their C-terminal function.

[0125] The peptides of the invention can be obtained by chemical or enzymatic synthesis from the constituent amino acids or their derivatives.

[0126] The peptides of the invention can finally be obtained by biotechnology (use of a microorganism modified or not by genetic engineering).

[0127] A person skilled in the art, knowing the business of extracting and purifying peptides and proteins, will be able to easily consider other processes for obtaining the peptides used in the composition.

[0128] The peptides used in the composition may in particular be chosen from an EGF (epidermal growth factor) peptide, VEGF (vascular endothelial growth factor), FGF (fibroblast growth factor), PDGF (platelet-derived growth factor), or N-acylamino-amide compounds that inhibit elastases.

[0129] Preferably, peptides with molecular weights ranging from 500 Da to 20 kDa are selected from N-acylamino-amide elastase inhibitor compounds and / or epidermal growth factor EGF of sequence SEQ ID No. 1.

[0130] According to a preferred embodiment, peptides with molecular weights ranging from 500 Da to 20 kDa are selected from N-acylamino-amide compounds that inhibit elastases.

[0131] The N-acylamino-amide elastase inhibitor compound according to the present invention may in particular be a compound of the following formula (I):

[0132] [Chem.l]

[0133] in which: - the radical Y represents O or S; - the radical Ri represents: (i) a hydrogen atom; (ii) a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having from 1 to 18 carbon atoms, optionally substituted by 1 to 5 groups, identical or different, chosen from -OH; -OR; -O-COR; -SH; -SR; -S-COR; -NH2; -NHR; -NRR'; -NH-COR; -Hal (halogen); -CN; -COOR; -COR; -P(O)-(OR)2; and -SO2-OR; with R and R' representing, independently of each other, a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, containing 1 to 6 carbon atoms, possibly halogenated, or even perhalogenated, said radicals R and R' being able to form together with N a carbon ring of 5 or 6 links which may further comprise at least one heteroatom chosen from O, N and / or S in the ring, and / or which may be substituted by 1 to 5 groups, identical or different, chosen from -OH; -OR”; -O-COR”; -SH; -SR”; -S-COR”; -NH2; -NHR”; -NH-COR”; -Hal (halogen); -CN; -COOR”; -COR”; -C-Hal3 (halogen), in particular -CF3; with R' ' representing a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, containing 1 to 6 carbon atoms, possibly halogenated, or even perhalogenated; (iii) a radical chosen from among the radicals -OR; -NH2; -NHR; -NRR'; -NH-COR; -COOR; -COR; with R and R' representing, independently of each other, a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 6 carbon atoms, possibly halogenated, or even perhalogenated, said radicals R and R' being able to form together with N a carbon ring of 5 or 6 links which may further comprise at least one heteroatom chosen from O, N and / or S in the ring, and / or which may be substituted by 1 to 5 groups, identical or different, chosen from -OH; -OR”; -O-COR”; -SH; -SR”; -S-COR”; -NH2; -NHR”; -NH-COR”; -Hal (halogen); -CN; -COOR”; and -COR”; with R” representing a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 6 carbon atoms, possibly halogenated, or even perhalogenated; - the radical R2 represents a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 18 carbon atoms, possibly substituted by 1 to 5 groups, identical or different, chosen from -OH; -OR; -O-COR; -SH; -SR; -S-COR; -NH2; -NHR; -NRR”; -NH-COR; -Hal (halogen); -CN; -COOR; and -COR; with R and R' representing, independently of each other, a linear, branched or cyclic, saturated or unsaturated hydrocarbon radical having 1 to 6 carbon atoms, possibly halogenated, or even perhalogenated, said radicals R and R' being able to form together with N a carbon ring of 5 or 6 members which may further comprise at least one heteroatom chosen from O, N and / or S in the ring, and / or which may be substituted by 1 to 5 groups, identical or different, chosen from -OH; -OR”; -O-COR”; -SH; -SR”; -S-COR”; -NH2; - NHR”; -NH-COR”; -Hal (halogen); -CN; -COOR”; and -COR”; with R” representing a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 6 carbon atoms, possibly halogenated, or even perhalogenated; - the radical R3 represents a radical chosen from those of formula (II) or (III): -A-C6H(5 y)-By (II) -C6H(5 y)-By. (III) in which: • y is an integer between 0 and 5 inclusive; • y' is an integer between 0 and 5 inclusive; • A is a divalent hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 18 carbon atoms, possibly substituted by 1 to 5 groups, identical or different, chosen from -OH; -OR; -O-COR; -SH; -SR; -S-COR; -NH2; -NHR; -NRR'; -NH-COR; -Hal (halogen, or even perhalogen); -CN; -COOR; -COR; -NO2; and -SO2-OR; with R and R' representing, independently of each other, a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 6 carbon atoms, possibly halogenated, or even perhalogenated, said radicals R and R' can together with N form a carbon ring of 5 or 6 links which may further comprise at least one heteroatom chosen from O, N and / or S in the ring, and / or can be substituted by 1 to 5 groups, identical or different, chosen from -OH; -OR”; -O-COR”; -SH; -SR”; -S-COR”; -NH2; -NHR”; -NH-COR”; -Hal (halogen); -CN; -COOR”; and -COR”; with R” representing a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 6 carbon atoms, possibly halogenated, or even perhalogenated; • B is a divalent hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 18 carbon atoms, possibly substituted by 1 to 5 groups, identical or different, chosen from -OH; -OR; -O-COR; -SH; -SR; -S-COR; -NH2; -NHR; -NRR'; -NH-COR; -Hal (halogen, or even perhalogen); -C-Hal3 (halogen), in particular -CF3; -CN; -COOR; -COR; -NO2; and -SO2-OR; with R and R' representing, independently of each other, a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 6 carbon atoms, possibly halogenated, or even perhalogenated; said radicals R and R' can together form with N a carbon ring of 5 or 6 members which may further comprise at least one heteroatom chosen from O, N and / or S in the ring, and / or can be substituted by 1 to 5 groups, identical or different, chosen from -OH; -OR”; -O-COR”; -SH; -SR”; -S-COR”; -NH2; -NHR”; -NH-COR”; -Hal (halogen); -CN; -COOR”; and -COR”; with R” representing a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 6 carbon atoms, possibly halogenated, or even perhalogenated; - the radical X represents a radical chosen from -OH; -OR4; -NH2; -NHR4; -NR4R5; -SR4; -COOR4; and -COR4; with R4 and R5 representing, independently of each other, a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 6 carbon atoms, possibly substituted by 1 to 5 groups, identical or different, chosen from -OH; -OR; -O-COR; -SH; -SR; -S-COR; -NH2; -NHR; -NRR'; -NH-COR; -Hal (halogen, or even perhalogen); -CN; -COOR; and -COR; with R and R' representing, independently of each other, a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 6 carbon atoms, possibly halogenated, or even perhalogenated; said radicals R and R' can together with N form a carbon ring of 5 or 6 links which may further comprise at least one heteroatom chosen from O, N and / or S in the ring, and / or can be substituted by 1 to 5 groups, identical or different, chosen from -OH; -OR”; -O-COR”; -SH; -SR”; -S-COR”; -NH2; -NHR”; -NH-COR”; -Hal (halogen); -CN; -COOR”; and -COR”; with R” representing a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 6 carbon atoms, possibly halogenated, or even perhalogenated; said radicals R4 and R5 can together with N form a carbon ring of 5 or 6 links which can further comprise at least one heteroatom chosen from O, N and / or S in the ring, and / or can be substituted by 1 to 5 groups, identical or different, chosen from -OH; -OR”; -O-COR”; -SH; -SR”; -S-COR”; -NH2; -NHR”; -NH-COR”; -Hal (halogen); -CN; -COOR”; and -COR”; with R” representing a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 6 carbon atoms, possibly halogenated, or even perhalogenated; its mineral or organic acid salts, its optical isomers, in isolated form or in racemic mixture.

[0134] Preferably, the radical Y represents O and / or the radical X represents -OH.

[0135] According to a preferred embodiment, -Hal (halogen) is fluorine.

[0136] By hydrocarbon radical, linear, branched or cyclic, means in particular radicals of the alkyl, aryl, aralkyl, alkylaryl, alkenyl and alkynyl type.

[0137] The C6H5 group present in the radical R3 should be understood as an aromatic cyclic group.

[0138] Preferably, the radical Y represents an oxygen atom.

[0139] Preferably, the radical Ri represents a hydrogen atom or a hy radical drocarbon, linear, branched or cyclic, saturated or unsaturated, having 1 to 12, and in particular 1, 2, 3, 4, 5 or 6, carbon atoms, possibly substituted.

[0140] In particular, the substituents can be chosen from -OH, -OR and / or -P(O)-(OR)2 with R representing a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, containing 1 to 6 carbon atoms, possibly halogenated, or even per-halogenated.

[0141] Preferably, the radical Ri represents a methyl, ethyl, propyl or isopropyl radical, optionally substituted by a -OH or -P(O)-(OR)2 group with R representing a methyl, ethyl, propyl or isopropyl radical.

[0142] Preferably, the radical R2 represents a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, containing from 1 to 12, and in particular 1, 2, 3, 4, 5 or 6 carbon atoms, optionally substituted.

[0143] In particular, the substituents can be chosen from -OH or -OR with R representing a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, containing 1 to 6 carbon atoms, possibly halogenated, or even perhalogenated.

[0144] Preferably, the radical R2 represents a methyl, ethyl, propyl, isopropyl, n-butyl, tert-butyl or isobutyl radical.

[0145] Preferably, the radical R3 represents a radical of the formula -C6H(3vJ-Bv), in which y' = 1, 2, or 3; or a radical of the formula -A-C6H(5y)-By in which y = 0, 1, or 2. Preferably, A is a divalent hydrocarbon radical, linear, branched, or cyclic, saturated or unsaturated, containing 1 to 12 carbon atoms, optionally substituted. The substituents of A are preferably chosen from -Hal (halogen, or even perhalogen); -CN; -COOR; -NO2; -SO2-OR; with R representing a hydrocarbon radical, linear, branched, or cyclic, saturated or unsaturated, containing 1 to 6 carbon atoms, optionally halogenated, or even perhalogenated.

[0146] Preferably, the radical R3 represents a group chosen from one of the following formulas:

[0147] [Chem.2]

[0148] in which A and B have the meanings indicated above.

[0149] In particular, the divalent radical A can be methylene, ethylene, propylene.

[0150] Radical B is preferably a methyl, ethyl, propyl, or isopropyl radical, substituted by one or more halogens, in particular chlorine, bromine, iodine, or fluorine, and preferably fully halogenated (perhalogenated), such as perfluorinated. The perfluoromethyl radical (-CF3) may be mentioned in particular as especially preferred.

[0151] Preferably, the radical X represents a radical chosen from -OH or -OR4 with R4 representing a hydrocarbon radical, linear, cyclic, or branched, saturated or unsaturated, containing 1 to 6 carbon atoms, optionally substituted. The substituents may be chosen from -OH and -OR, with R representing a hydrocarbon radical, linear, branched, or cyclic, saturated or unsaturated, containing 1 to 6 carbon atoms, optionally halogenated or even perhalogenated. Preferably, radical X represents a radical chosen from -OH, -OCH3, -OC2H5, -O-C3H7, or -OC4H9.

[0152] Preferably, the N-acylamino-amide elastase inhibitor compound is at least N-acetyl-3-trifluoromethyl-phenyl-(valine-glycine).

[0153] In the context of the present invention, the term "N-acetyl-3-trifluoromethyl-phenyl-(valine-glycine)" covers, in particular, the basic motif of the following formula and its derivative:

[0154] [Chem.3]

[0155] The term "N-acetyl-3-trifluoromethyl-phenyl-(valine-glycine) or one of its derivatives" also includes, within the scope of the present invention, salts of N-acetyl-3-trifluoromethyl-phenyl-(valine-glycine), and in particular salts of alkali metals such as sodium salt and potassium salt.

[0156] N-acetyl-3-trifluoromethyl-phenyl-(valine-glycine) is an anti-aging agent.

[0157] According to embodiments of the electrical method, the method further comprises the transdermal delivery of a composition comprising a peptide with a molecular weight ranging from 500 Da to 20 kDa, in particular an N-acylamino-amide compound that inhibits elastases, in particular one or more of the N-acetyl-3-trifluoromethyl-phenyl-(valine-glycine), N-acetyl-3-trifluoromethyl-phenyl-(valine-glycine) derivatives, N-acetyl-3-trifluoromethyl-phenyl-(valine-glycine) ions, and N-acetyl-3-trifluoromethyl-phenyl-(valine-glycine) derivative ions, present in quantities ranging from 0.1% to 20% by weight.

[0158] The peptide with a molecular weight ranging from 500 Da to 20 kDa, in particular the N-acylamino-amide compound inhibiting elastases, especially N-acetyl-3-trifluoromethyl-phenyl-(valine-glycine) or a derivative thereof, may be present in the composition according to the present invention in a content of between 0.2% and 10%, preferably between 0.5% and 5%, and more particularly between 0.8% and 2% by weight, relative to the total weight of the composition.

[0159] In one embodiment, the composition comprises 1% by weight of at least one peptide with a molecular weight ranging from 500 Da to 20 kDa, in particular of at least one N-acylamino-amide elastase inhibitor compound, and in particular of N-acetyl-3-trifluoromethyl-phenyl-(valine-glycine).

[0160] The compounds according to the invention can be easily prepared by a person skilled in the art based on their general knowledge. In particular, it is possible to react a carboxylic acid, an aldehyde, an amino compound, and an isonitrile according to the Ugi reaction.

[0161] It is understood that during the synthesis of the compounds according to the invention and depending on the nature of the different radicals present in the starting compounds, the specialist will take care to protect certain substituents so that they do not react during the reactions.

[0162] According to another preferred embodiment, the peptide with a molecular weight ranging from 500 Da to 20 kDa is at least the epidermal growth factor EGF of sequence SEQ IDN°1.

[0163] According to embodiments of the process, the process further comprises the transdermal delivery of a composition comprising the epidermal growth factor EGF of sequence SEQ ID No. 1, present in an amount ranging from 0.2% to 10% by weight.

[0164] Epidermal growth factor EGF of sequence SEQ ID No. 1, may be present in the composition according to the present invention in a content of between 0.2% and 10%, preferably between 0.5% and 5%, and more particularly between 0.8% and 2% by weight, relative to the total weight of the composition.

[0165] In one embodiment, the composition comprises 1% by weight of epidermal growth factor EGF of sequence SEQ ID No. 1. Aqueous phase

[0166] A composition according to the invention preferably comprises an aqueous phase.

[0167] According to a preferred embodiment, the composition according to the present invention has a water content of between 20% and 100% by weight, in particular between 40% and 95% by weight, and preferably between 60% and 90% by weight, relative to the total weight of the composition.

[0168] According to a preferred embodiment, the aqueous phase of a composition according to the invention also comprises at least one alcohol, chosen in particular from polyols, especially chosen from glycols.

[0169] Thus, the composition may also include a polyol selected from propylene glycol, 1,3-propanediol, dipropylene glycol, butylene glycol, pentylene glycol, hexylene glycol, caprylyl glycol, glycerol and sugars such as sorbitol, (poly)alkylene glycols, and mixtures thereof.

[0170] Preferably, the composition may comprise a polyol selected from di-propylene glycol, caprylyl glycol and glycerol, and mixtures thereof.

[0171] According to one embodiment, the mass concentrations of polyol vary from 0.01% to 40% by weight, relative to the total weight of said composition.

[0172] Preferably, the mass concentrations of polyol range from 0.1% to 30%, and preferably from 5% to 15% by weight, relative to the total weight of said composition. Thickener / Gelding agent

[0173] According to preferred embodiments, a composition according to the present invention may include a thickener / gelling agent.

[0174] Thus, depending on the viscosity of the composition to be obtained, one or more thickeners / gelling agents, in particular hydrophilic, i.e. soluble or hydro-dispersible, can be incorporated into the composition.

[0175] Examples of hydrophilic gelling agents that may be mentioned include modified or unmodified carboxyvinyl polymers, such as the products marketed under the names Carbopol (CTFA name: carbomer) and Pemulen (CTFA name: Acrylates / Cio-30 alkyl acrylate crosspolymer) by Goodrich; polyacrylamides; polymers and copolymers of 2-acrylamido 2-methylpropane sulfonic acid, possibly crosslinked and / or neutralized, such as poly(2-acrylamido 2-methylpropane sulfonic acid) marketed by Hoechst under the name Hostacerin AMPS® (CTFA name: Ammonium poly-acryldimethyltauramide);crosslinked anionic copolymers of acrylamide and AMPS®, presented in the form of a Water-in-Oil emulsion, such as those marketed under the name Sepigel 305 (CTFA name: Polyacrylamide / Ci3-i4 Iso-paraffin / Laureth-7) and under the name Simulgel 600 (CTFA name: Acrylamide / Sodium acryloyldimethyltaurate copolymer / Isohexadecane / Polysorbate 80) by the company SEPPIC; Polysaccharide biopolymers such as modified celluloses, carrageenans, particularly kappa-carrageenan, gellan gum, agar-agar, xanthan gum, alginate-based compounds, especially sodium alginate, scleroglucan gum, guar gum, inulin and pullulan, cassia gum, karaya gum, konjac gum, tragacanth gum, tara gum, acacia gum or gum arabic, and mixtures thereof. The quantity of gelling agents depends on the desired purpose.

[0176] According to a preferred embodiment, a composition according to the present invention comprises a polysaccharide, in particular selected from cellulose or a derivative thereof, in particular cellulose ethers or esters.

[0177] Cellulose derivatives can be anionic, cationic, amphoteric, or nonionic. Among these derivatives, a distinction is made between cellulose ethers, cellulose esters, and cellulose ester ethers.

[0178] Among nonionic cellulosic ethers, examples include alkyl-celluloses such as methylcelluloses and ethylcelluloses, hydroxyalkyl-celluloses such as hydroxymethylcelluloses, hydroxyethylcelluloses and hydroxypropylcelluloses, and mixed hydroxyalkylalkylcelluloses such as hydroxypropylmethylcelluloses, hydroxyethylmethylcelluloses, hydroxyethylethylcelluloses and hydroxybutylmethylcelluloses.

[0179] Cellulose and derivatives are represented, for example, by the products sold under the names Avicel® (microcrystalline cellulose, MCC) by FMC Biopolymers, under the name Cekol (carboxymethylcellulose) by Noviant (CP-Kelco), under the name Akucell AF (sodium carboxymethylcellulose) by Akzo Nobel, under the names Methocel™ (cellulose ethers) and Ethocel™ (ethylcellulose) by Dow, and under the names Aqualon® (carboxymethylcellulose and sodium carboxymethylcellulose), Benecel® (methylcellulose), Blanose™ (carboxymethylcellulose), Culminai® (methylcellulose, hydroxypropylmethylcellulose), Klucel® (hydroxypropylcellulose), Polysurf® (cetylhydroxyethylcellulose) and Natrosol® CS (hydroxyethylcellulose) by Hercule Aqualon.

[0180] According to a preferred embodiment, a composition according to the invention comprises at least one hydroxypropylmethylcellulose and / or a crosslinked anionic copolymer of acrylamide and AMPS®.

[0181] According to a preferred embodiment, a composition according to the invention comprises at least one hydroxypropylmethylcellulose.

[0182] According to a preferred embodiment, a composition according to the invention comprises at least one crosslinked anionic copolymer of acrylamide and AMPS®.

[0183] In particular, the quantity of thickeners / gelling agents varies, for example, from 0.01 % to 10%, for example from 0.1% to 5% by weight, relative to the total weight of the composition. Oily phase

[0184] As mentioned above, a composition according to the invention may include an oily phase.

[0185] When the composition used according to the invention includes an oily phase, it preferably contains at least one oil, in particular a cosmetic oil. It may also contain other fatty substances.

[0186] Among the oils that can be used in the composition of the invention, mention may be made of hydrocarbon oils of animal origin, hydrocarbon oils of vegetable origin, synthetic esters and ethers, in particular of fatty acids, hydroxylated esters, polyol esters, pentaerythritol esters, linear or branched hydrocarbons of vegetable, mineral or synthetic origin, fatty alcohols and fatty acids containing from 8 to 26 carbon atoms, fluorinated silicone and / or par- silicone oils and their mixtures are highly hydrogenated.

[0187] According to a preferred embodiment, a composition according to the invention comprises at least one silicone oil.

[0188] Silicone oils can, for example, be chosen from among volatile or non-volatile, linear or cyclic polydimethylsiloxanes (PDMS) which are liquid or pasty at room temperature, in particular cylopolydimethylsiloxanes (cyclomethicones) such as cyclohexasiloxane; polydimethylsiloxanes having alkyl, alkoxy or phenyl groups, during or at the end of the silicone chain, the groups having from 2 to 24 carbon atoms; phenyl silicones such as phenyl trimethicones, phenyl dimethicones, phenyl trimethylsiloxy diphenyl siloxanes, diphenyl dimethicones, diphenyl methyldiphenyl trisiloxanes or 2-phenyl ethyl trimethylsiloxysilicates, and polymethylphenylsiloxanes.

[0189] According to a preferred embodiment, a composition according to the invention comprises at least one cyclohexasiloxane oil.

[0190] Other fatty substances that may be present in the oily phase are, for example, fatty acids comprising 8 to 30 carbon atoms, for example stearic acid, lauric acid, palmitic acid and oleic acid; waxes, for example lanolin wax, beeswax, carnauba wax or candelilla wax, paraffin wax, lignite wax or microcrystalline waxes, ceresin or ozokerite, and synthetic waxes, for example polyethylene waxes and Fischer-Tropsch waxes; silicone resins such as trifluoromethyl-(Ci-C4) alkyl dimethicone and trifluoropropyl dimethicone; and silicone elastomers.

[0191] These fats can be chosen in a variety of ways by a person skilled in the art in order to prepare a composition having the desired properties, for example in terms of consistency or texture.

[0192] According to a preferred embodiment, a composition according to the invention comprises at least one silicone elastomer.

[0193] The term “silicone elastomer” or “organopolysiloxane elastomer” refers to a flexible, deformable organopolysiloxane with viscoelastic properties, notably having the consistency of a sponge or a soft sphere. Its modulus of elasticity is such that this material resists deformation and has a limited capacity to expand and contract. This material is capable of returning to its original shape after stretching.

[0194] This is more specifically a cross-linked organopolysiloxane elastomer.

[0195] In particular, the silicone elastomer used in the present invention is selected from Dimethicone Crosspolymer (INCI name), Vinyl Dimethicone Crosspolymer (INCI name), Dimethicone / Vinyl Dimethicone Crosspolymer (INCI name), Dimethicone Crosspolymer-3 (INCI name).

[0196] According to a preferred embodiment, the composition according to the invention comprises at least one crosslinked silicone elastomer with the INCI name "dimethicone crosspolymer" or "dimethicone (and) dimethicone crosspolymer", preferably with a dimethicone of viscosity ranging from 1 to 100 est, in particular from 1 to 10 est at 25 °C, such as the Hexadiene / Polydimethylsiloxane crosslinked blend (5 est) marketed under the name DC 9041® by Dow Corning or the Hexadiene / Polydimethylsiloxane crosslinked blend (2 est) marketed under the name EL-9240® by Dow Corning.

[0197] The silicone elastomer may be present in a composition according to the invention in a content of between 0.1% and 20% by weight, in particular between 0.5% and 10% by weight, and more particularly between 1% and 5% by weight, relative to the total weight of the composition.

[0198] In particular, the quantity of oil phase can vary, for example, from 0% to 30%, and more particularly from 0.1% to 15% by weight, relative to the total weight of the composition. T-active agent / Emulsifier

[0199] According to one embodiment, the composition according to the invention may also include at least one emulsifier.

[0200] Examples of emulsifiers that can be used in emulsions include non-ionic emulsifiers such as oxyalkylated (more particularly polyoxyethylated) fatty acid esters of glycerol; oxyalkylated fatty acid esters of sorbitan; oxyalkylated fatty acid esters (oxyethylated and / or oxypropylened); oxyalkylated fatty alcohol ethers (oxyethylated and / or oxypropylened); sugar esters such as sucrose stearate; and mixtures thereof, such as the mixture of glyceryl stearate and PEG-40 stearate.

[0201] We can also mention fatty alcohol / alkylpolyglycoside emulsifying mixtures as described in patent applications WO 92 / 06778, WO 95 / 13863 and WO 98 / 47610, for example the commercial products sold by the company SEPPIC under the name Montanov®.

[0202] Among the emulsifiers that can be used in the compositions according to the invention, examples include alkyl dimethicone copolyols, for example Cetyl PEG / PPG-10 / 1 Dimethicone and more particularly the mixture Cetyl PEG / PPG-10 / 1 Dimethicone and Dimethicone (INCI name), such as the product sold under the brand name Abil EM90 by the company Goldschmidt, or the mixture (Polyglyceryl-4 stearate and Cetyl PEG / PPG-10 (and) Dimethicone (and) Hexyl Laurate), such as the product sold under the brand name Abil WE09 by the same company.

[0203] Dimethicone copolyols can also be mentioned, for example PEG-18 / PPG-18 Dimethicone and more particularly the mixture Cyclopentasiloxane (and) PEG-18 / PPG-18 Dimethicone (INCI name), such as the product sold by Dow Corning under the brand name Silicone DC 5225 C or KF-6040 by Shin-Etsu.

[0204] We can also mention non-ionic emulsifiers derived from fatty acids and polyols, alkyl polyglycosides (APGs) and sugar esters, as well as mixtures thereof.

[0205] As non-ionic emulsifiers derived from fatty acids and polyols, fatty acid esters of polyols may be used in particular, the fatty acid containing in particular a C8-C24 alkyl chain, and the polyols being, for example, glycerol and sorbitan.

[0206] Fatty acid esters of polyols which may be specifically mentioned are isostearic acid esters of polyols, stearic acid esters of polyols and mixtures thereof, in particular isostearic acid esters of glycerol and / or sorbitan.

[0207] Stearic acid esters of polyols that may be specifically mentioned include polyethylene glycol esters, for example PEG-30 dipolyhydroxystearate, such as the product sold under the name Arlacel P135 by the company ICI.

[0208] Examples of glycerol and / or sorbitan esters that may be mentioned include polyglyceryl isostearate, such as the product sold under the name Isolan GI 34 by Goldschmidt; sorbitan isostearate, such as the product sold under the name Arlacel 987 by ICI; sorbitan glyceryl isostearate, such as the product sold under the name Arlacel 986 by ICI, the mixture of sorbitan isostearate and polyglyceryl isostearate (3 mol) sold under the name Arlacel 1690 by Uniqema, and mixtures thereof.

[0209] The emulsifier can also be chosen from alkylpolyglycosides having an HLB of less than 7, for example those represented by the general formula (1) RO-(G)x (1), in which R represents a branched and / or unsaturated alkyl radical comprising 14 to 24 carbon atoms, G represents a reduced sugar comprising 5 or 6 carbon atoms, and x is a value from 1 to 10 and preferably from 1 to 4, and G designates in particular glucose, fructose or galactose.

[0210] The unsaturated alkyl radical may comprise one or more ethylenically unsaturated groups, and in particular one or two ethylenically unsaturated groups.

[0211] Among alkyl polyglycosides of this type, alkyl polyglucosides (G = glucose in formula (I)) may be cited, and in particular compounds of formula (I) in which R represents more particularly an oleyl radical (unsaturated radical at C[8]) or isostearyl radical (saturated radical at C18), G designates glucose, x is a value from 1 to 2, in particular isostearyl glucoside or oleyl glucoside, and mixtures thereof. This alkyl polyglucoside can be used in a mixture with a coemulsifier, more particularly with a fatty alcohol and in particular a fatty alcohol containing the same fatty chain as that of the alkyl polyglucoside, i.e. comprising 14 to 24 carbon atoms and containing a branched and / or unsaturated chain, for example isostearyl alcohol when the alkylpolyglucoside is isostearyl glucoside, and oleyl alcohol when the alkylpolyglucoside is oleyl glucoside, possibly in the form of a self-emulsifying composition, such as described, for example, in document WO-A-92 / 06778. One can use, for example, the mixture of isostearyl glucoside and isostearyl alcohol, sold under the name Montanov WO 18 by the company SEPPIC, as well as the mixture of octyldodecanol and octyldodecyl xyloside sold under the name Fludanov 20X by the company SEPPIC.

[0212] We can also mention succinic-terminated polyolefins, for example succinic-terminated esterified polyisobutylenes and their salts, in particular diethanolamine salts, such as the products sold under the names Lubrizol 2724, Lubrizol 2722 and Lubrizol 5603 by the Lubrizol company or the commercial product Chemcinnate 2000.

[0213] According to a preferred embodiment, the composition according to the invention comprises at least one non-ionic emulsifier, preferably chosen from stearic acid esters of polyols and / or alkyl polyglycosides.

[0214] The total quantity of emulsifiers in the composition will preferably, in a composition according to the invention, be in active matter contents ranging from 0.5% to 8% by weight, and more particularly from 1% to 6% by weight, relative to the total weight of the composition. Base

[0215] In embodiments of electroporation composition, the composition may further comprise at least one base.

[0216] The base can be chosen from mineral bases, for example alkali metal hydroxides, sodium hydroxide, potassium hydroxide, ammonium hydroxides, ammonia, organic bases, for example monoethanolamine, diethanolamine, triethanolamine, triisopropylamine, tris[(2-hydroxy)l-propyl)]amine, N,N-dimethylethanolamine, 2-amino 2-methyl 1-propanol, 2-amino 2-methyl 1,3-propanediol, triethylamine, 1a-dimethylaminopropylamine and amphoteric bases (i.e. bases having both anionic and cationic functional groups), such as primary, secondary, tertiary or cyclic organic amines, and amino acids. Examples of amphoteric bases include glycine, lysine, arginine, taurine, histidine, alanine, valine, cysteine, trihydroxymethylaminomethane (TRISTA), triethanolamine, and any mixture thereof.

[0217] According to a particular embodiment, the base of the composition is chosen from sodium hydroxide, potassium hydroxide, ammonium hydroxides, ammonia, monoethanolamine, diethanolamine, triethanolamine, tro- methamphetamine, and any of their mixtures.

[0218] According to a particular embodiment, the basis of the composition is sodium hydroxide.

[0219] According to a particular embodiment, the base of the composition according to the invention is present at a concentration by weight of less than 0.5% by weight, or even less than 0.3% by weight, relative to the total weight of the composition. Other additives

[0220] The cosmetic composition may also include at least one additive selected from typical cosmetic adjuvants, such as hydrophilic or lipophilic gelling agents, water-soluble or liposoluble active agents, for example anti-aging active agents, film-forming polymers, preservatives, sequestrants, antioxidants, solvents, perfumes, odor absorbers, pH correctors, and mixtures thereof.

[0221] According to one embodiment, the composition according to the invention may also include at least one preservative, preferably phenoxyethanol.

[0222] A person skilled in the art shall take care to choose the optional additional adjuvants and / or their quantity in such a way that the advantageous properties of the composition are not, or not substantially, affected by the envisaged addition. Physiologically acceptable environment

[0223] The composition, in particular the cosmetic composition, according to the invention, comprises a physiologically acceptable medium.

[0224] For the purposes of the present invention, the expression "physiologically acceptable medium" is intended to designate a medium suitable for the topical administration of a composition.

[0225] A physiologically acceptable medium generally has no unpleasant odor or appearance and is entirely compatible with topical administration. In the present case, when the composition is intended for topical administration, i.e., by application to the surface of the keratinous material in question, such a medium is considered physiologically acceptable in particular when it does not cause tingling, pulling, or redness unacceptable to the user.

[0226] In particular, the composition is suitable for topical application, i.e., application to the surface of the skin, scalp and / or mucous membrane in question. Thus, the physiologically acceptable medium is preferably a cosmetically or dermatologically acceptable medium, i.e., a medium that has no unpleasant odor, color or appearance, and that does not cause unacceptable tingling, tightness or redness in the user.

[0227] The composition may then include any constituent normally used in the intended application.

[0228] Of course, a person skilled in the art will take care to choose the optional additional compound(s), and / or their quantity, in such a way that the advantageous properties of the compounds according to the invention are not, or are not substantially, affected by the envisaged addition.

[0229] Unless otherwise indicated, the quantities shown are expressed as mass percentages. Example

[0230] To test the effect of the device, a sample of human skin is fixed by its periphery to a support, with the counter electrode of the electroporation device interposed between the inner surface of the skin and the support. The electrode of the electroporation device is placed in contact with the outer surface of the skin sample. The housing of the electroporation device is immobilized by a support. The support is placed on an orbital shaker, so that the electrode moves across the surface of the skin.

[0231] The device used in this example is a BTX Gemini X2 programmable signal generator (Harvard Instruments).

[0232] The electroporation treatment lasts approximately 1 minute. It consists of 81 pulses of 10 ms each, with rest periods of 500 ms between pulses. The polarity is negative, meaning the electrode is at a negative potential relative to the counter electrode. On the skin, the voltage between the electrode and the counter electrode is approximately 40 V.

[0233] 50 pL of EGF is applied before the device is installed (corresponding to 100 pL / cm2).

[0234] EGF is applied here independently of the N- compound acetyl-3-trifluoromethyl-phenyl-(valine-glycine).

[0235] The EGF stock solution is prepared by dissolving the synthetic peptide powder in PBS at a concentration of 2.50 pg / mL prior to the experiment, where 125 ng are applied per cm2 of skin explant.

[0236] For the compound N-acetyl-3-trifluoromethyl-phenyl-(valine-glycine), 100 pL / cm2 of each formulation 1 and 2 are applied before treating the skin with the Fusion Meso Xpert mode S.

[0237] The two cosmetic compositions are prepared according to the following protocols:

[0238] For the preparation of composition 1, 95% (qs.) of deionized water is weighed. 7% glycerin and 2% dipropylene glycol are added. The mixture is stirred at 350 rpm. 1% N-acetyl-3-trifluoromethyl-phenyl-(valine-glycine) and 1% hydroxypropyl methylcellulose are weighed and then gradually added to the mixture while stirring to disperse the powder. 0.5% phenoxyethanol is added. The mixture is stirred at 550 rpm for 15 minutes. The pH is adjusted to 5.5 with sodium hydroxide. The remaining deionized water (q.s.p. 100%) is added to reach the desired weight. Composition 1 is a gel.

[0239] To prepare composition 2, phase A is mixed and heated to 50 °C to solubilize the active ingredient. Phase B is added. The oily phase C is mixed and heated to 30 °C. It is then incorporated into the mixture of phases A and B all at once. The mixture is stirred slowly with a spatula. Diffusion is observed, and the mixture is stirred until an emulsion is obtained. The mixture is then stirred for a few minutes using a deflocculator. Phase D is added. Composition 2 is an oil-in-water emulsion.

[0240] The compositions have the following formulations (quantities are expressed by weight, relative to the total weight of the composition):

[0241] [Tables 1] Phases Composés (Nom INCI) Formulation 1 (% en poids) Formulation 2 (% en poids) A Water (EAU DESIONTSFE MICROBIOLOGIQUEMENT PROPRE) qsp Î00 qsp 100 Sodium Hydtoxide (CAUSTIC LYE, GUI ARAT ALKALIES AND CHEMICALS) 0,24 0,11 Acetyl Trifluoromethylphenyl ValyiGlyciae (MEXORYL SAR, CHLMEX) 1 1 PhenoxyethaBol (sepicide LD, SEPPIC) 0,5 0,5 Dipropyleae Glycol (DIPROPYLENE-GLYCOL CARE. BASF) A 2 Glycenn (ECOCEROL, ECOGREEN OLEOCHEMICALS1 7 7 Capjylyl Glycol (HYDROLTTE CG®. SYMRISE) 0,7 B PEG-30 Dipolyhydroxystearare icithrol dphs-SO-fMVj. CRODA) 0,5 Octyldodecauol (and) Octyldodecyl Xyloside (FLUIDANOV 20X® ( SEPPIC » 2 C Cyclohexasiloxane (XIAMETER PMX-0246 CY'CLOHEXASILOXANE, DOW CORNING, DOW CHEMICAL) 6 Dimethicone Crosspolymer (DOWSIL EL-9240 SILICONE ELASTOMER BLEND, DOW CORNING, DOW CHEMICAL) 2 D Hydroxyprcpyl MetbylcelMose (METHOCEL F 4 M PERSONAL CARE GRADE) 1 Sodium Acrylate / Sodium Acryloyldimeîhyl Taurate Copolymer (and) Isohëxadecane taud) Polysorbate 80 fsiMULGEL EG, SEPPIC) 5 Comparative example

[0242] On the one hand, compositions 1 and 2 are applied topically and on the other hand, their application is combined with electroporation. Results

[0243] The skin is extracted from the experimental system and then analyzed to determine the amount of N-acetyl-3-trifluoromethyl-phenyl-(valine-glycine) that has penetrated through a Elisa's technique.

[0244] The results are given in [Fig.4] and in [Fig.5].

[0245] It is demonstrated that, thanks to the process according to the invention, the amount of N-acetyl-3-trifluoromethyl-phenyl-(valine-glycine) that has penetrated is much higher (higher log on [Fig.5]), compared to the topical application of an identical composition.

[0246] Throughout the description, including the claims, the expression "comprising one" shall be understood as synonymous with "comprising at least one", unless otherwise specified.

[0247] The expressions "between ... and ...", "includes from ... to ...", "consisting of ... to ...", and "ranging from ... to ..." must be understood inclusively, unless otherwise specified.

[0248] List of sequences

[0249] SEQIDN°1

[0250] NSDSECPLSHDGYCLHDGVCMYIEALDKYACNCVVGYIGERCQYRDLKWW E

Claims

Demands

1. Electroporation process for delivering a composition through human keratinous materials, the composition comprising at least one peptide with a molecular weight ranging from 500 Da to 20 kDa, the electroporation process comprising exposing the composition in contact with said keratinous materials to a succession of pulses of an electric current, the electric current being supplied by an electroporation device having at least one electrode (2) and at least one counter electrode (3), the pulses each having a duration (tpuise) of between 1 ms and 5 s, with a rest interval (Toff) between them of between 0.1 s and 5 s, and the electric current having a voltage amplitude of between 20 V and 400 V, better from 25 V to 300 V, even better from 30 V to 200 V and an intensity of between 0.1 mA and 10 mA.

2. Method according to claim 1, the duration (tpUke) of a pulse being between 5 ms and 3 s, even better between 10 ms and 2 s.

3. A method according to any one of the preceding claims, the rest interval (Toff) being between 0.3 s and 3 s, and even better between 0.5 s and 2 s.

4. Method according to any one of the preceding claims, the voltage range from 25 V to 300 V, or even better from 30 V to 200 V.

5. A method according to any one of the preceding claims, the intensity ranging from 0.2 mA to 2 mA, and even better from 0.25 mA to 1 mA.

6. A method according to any one of the preceding claims, the number N of consecutive pulses applied being between 2 and 15000, better between 10 and 5000, still better between 50 and 500.

7. Electroporation process according to any one of the preceding claims, the applied current having a duty cycle (tpUke / (tpUke+T off)) varying from 10% to 90%, preferably from 20% to 80%, where tpUke denotes the duration of a pulse and Toff the interval between two successive pulses.

8. Electroporation process according to any one of the preceding claims, the electric current having a direct polarity, the polarity of the electrode being in particular negative with respect to that of the counter electrode.

9. Electroporation method according to any one of the preceding claims, the surface of the electrode(s) (2) in contact with the keratinous materials varying from 2 to 20 cm2.

10. Electroporation process according to any one of the preceding claims, the counter electrode being static and having a surface area in contact with human keratinous materials greater than that of the electrode, which is displaced in contact with the keratinous materials, the surface area of ​​the counter electrode preferably being greater than 1.5 times that of the electrode.

11. Electroporation process according to any one of the preceding claims, the maximum open-circuit voltage between electrode (2) and counter electrode (3) ranging from 150 V to 250 V.

12. Electroporation method according to any one of the preceding claims, consisting of manually moving the electrode(s) (2) of the electroporation device over the keratinous materials while subjecting the latter to said electric current pulses.

13. Electroporation process according to any one of the preceding claims, the electric current being of square or rectangular waveform.

14. Electroporation method according to any one of the preceding claims, the electroporation device (1) being hand-held.

15. Electroporation process according to any one of the preceding claims, comprising a topical application of the composition to the area to be treated before the application of the electric current and / or during said application.

16. Electroporation process according to any one of the preceding claims, the electrode(s) (2) having a rounded surface for contact with keratinous materials.

17. Electroporation process according to any one of the preceding claims, characterized in that the peptide with a molecular weight ranging from 500 Da to 20 kDa is selected from N-acylamino-amide compounds that inhibit elastases.

18. Electroporation process according to any one of the preceding claims, characterized in that the peptide with a molecular weight ranging from 500 Da to 20 kDa is selected from the N-acylamino-amide elastase-inhibiting compounds of formula (I): in which: - the radical Y represents O or S; - the radical Ri represents: (i) a hydrogen atom; (ii) a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having from 1 to 18 carbon atoms, optionally substituted by 1 to 5 groups, identical or different, selected from -OH; -OR; -O-COR; -SH; -SR; -S-COR; -NH2; -NHR; -NRR'; -NH-COR; -Hal (halogen); -CN; -COOR; -COR; -P(O)-(OR)2; and -SO2-OR; with R and R' representing, independently of each other, a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, containing 1 to 6 carbon atoms, possibly halogenated, or even per-halogenated, said radicals R and R' being able to form together with N a carbon ring of 5 or 6 links which may further comprise at least one heteroatom chosen from O, N and / or S in the ring, and / or which may be substituted by 1 to 5 groups, identical or different, chosen from -OH; -OR”; -O-COR”; -SH; -SR”; -S-COR”; -NH2; -NHR”; -NH-COR”; -Hal (halogen); -CN; -COOR”; -COR”; -C-Hal3 (halogen), in particular -CF3; with R” representing a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, containing 1 to 6 carbon atoms, possibly halogenated, or even perhalogenated; (iii) a radical chosen from among the radicals -OR; -NH2; -NHR; -NRR'; -NH-COR; -COOR; -COR; with R and R' representing, independently of each other, a linear, branched or cyclic, saturated or unsaturated hydrocarbon radical having 1 to 6 carbon atoms, possibly halogenated, or even perhalogenated, said radicals R and R' being able to form together with N a carbon ring of 5 or 6 members which may further comprise at least one heteroatom chosen from O, N and / or S in the ring, and / or which may be substituted by 1 to 5 groups, identical or different, chosen from -OH; -OR”; -O-COR”; -SH; -SR”; -S-COR”; -NH2; -NHR”; - NH-COR”; -Hal (halogen); -CN; -COOR”; and -COR”; with R” representing a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 6 carbon atoms, possibly halogenated, or even perhalogenated; - the radical R2 represents a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 18 carbon atoms, possibly substituted by 1 to 5 groups, identical or different, chosen from -OH; -OR; -O-COR; -SH; -SR; -S-COR; -NH2; -NHR; -NRR”; -NH-COR; -Hal (halogen); -CN; -COOR; and -COR; with R and R' representing, independently of each other, a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 6 carbon atoms, possibly halogenated, or even perhalogenated, said radicals R and R' being able to form together with N a carbon ring of 5 or 6 members which may further comprise at least one heteroatom chosen from O, N and / or S in the ring, and / or may be substituted by 1 to 5 groups, identical or different, chosen from -OH; -OR”; -O-COR”; -SH; -SR”; -S-COR”; -NH2; -NHR”; -NH-COR”; -Hal (halogen); -CN; -COOR”; and -COR”;with R” representing a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 6 carbon atoms, possibly halogenated, or even perhalogenated; - the radical R3 represents a radical chosen from those of formula (II) or (III): -A-C6H(5 y)-By (II) -C6H(5 y)-By. (III) in which: • y is an integer between 0 and 5 inclusive; • y' is an integer between 0 and 5 inclusive; • A is a divalent hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 18 carbon atoms, possibly substituted by 1 to 5 groups, identical or different, chosen from -OH; -OR; -O-COR; -SH; -SR; -S-COR; -NH2; -NHR; -NRR'; -NH-COR; -Hal (halogen, or even perhalogen); -CN; -COOR; -COR; -NO2; and -SO2-OR; with R and R' representing, independently of each other, a linear, branched or cyclic hydrocarbon radical, saturated or unsaturated, having 1 to 6 carbon atoms, possibly halogenated, or even perhalogenated, said radicals R and R' being able to form together with N a ring carbon with 5 or 6 links which may further comprise at least one heteroatom chosen from O, N and / or S in the ring, and / or which may be substituted by 1 to 5 groups, identical or different, chosen from -OH; -OR”; -O-COR”; -SH; -SR”; -S-COR”; -NH2; -NHR”; -NH-COR”; -Hal (halogen); -CN; -COOR”; and -COR”; with R” representing a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 6 carbon atoms, possibly halogenated, or even perhalogenated; • B is a divalent hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 18 carbon atoms, possibly substituted by 1 to 5 groups, identical or different, chosen from -OH; -OR; -O-COR; -SH; -SR; -S-COR; -NH2; -NHR; -NRR'; -NH-COR; -Hal (halogen, or even perhalogen); -C-Hal3 (halogen), in particular -CF3; -CN; -COOR; -COR; -NO2; and -SO2-OR; with R and R' representing, independently of each other, a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 6 carbon atoms, possibly halogenated, or even perhalogenated; said radicals R and R' can together with N form a carbon ring of 5 or 6 links which may further comprise at least one heteroatom chosen from O, N and / or S in the ring, and / or can be substituted by 1 to 5 groups, identical or different, chosen from -OH; -OR”; -O-COR”; -SH; -SR”; -S-COR”; -NH2; -NHR”; -NH-COR”; -Hal (halogen); -CN; -COOR”; and -COR”; with R” representing a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 6 carbon atoms, possibly halogenated, or even perhalogenated; - the radical X represents a radical chosen from -OH; -OR4; -NH2; -NHR4; -NR4R5; -SR4; -COOR4; and -COR4; with R4 and R5 representing, independently of each other, a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 6 carbon atoms, possibly substituted by 1 to 5 groups, identical or different, chosen from -OH; -OR; -O-COR; -SH; -SR; -S-COR; -NH2; -NHR; -NRR'; -NH-COR; -Hal (halogen, or even perhalogen); -CN; -COOR; and -COR; with R and R' representing, independently of each other, a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 6 carbon atoms, possibly halogenated, or even perhalogenated; said radicals R and R' can together form a cycle carbon with 5 or 6 links which may further comprise at least one heteroatom chosen from O, N and / or S in the ring, and / or which may be substituted by 1 to 5 groups, identical or different, chosen from -OH; -OR”; -O-COR”; -SH; -SR”; -S-COR”; -NH2; -NHR”; -NH-COR”; -Hal (halogen); -CN; -COOR”; and -COR”; with R” representing a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 6 carbon atoms, possibly halogenated, or even perhalogenated; said radicals R4 and R5 being able to form together with N a carbon ring of 5 or 6 links which may further comprise at least one heteroatom chosen from O, N and / or S in the ring, and / or which may be substituted by 1 to 5 groups, identical or different, chosen from -OH; -OR”; -O-COR”; -SH; -SR”; -S-COR”; -NH2; -NHR”; -NH-COR”; -Hal (halogen); -CN; -COOR”; and -COR”;with R” representing a hydrocarbon radical, linear, branched or cyclic, saturated or unsaturated, having 1 to 6 carbon atoms, possibly halogenated, or even perhalogenated; its mineral or organic acid salts, its optical isomers, in isolated form or in racemic mixture.;

19. Electroporation process according to any one of the preceding claims, characterized in that the peptide with a molecular weight ranging from 500 Da to 20 kDa is at least N-acety 1-3-trifluoromethyl 1-pheny 1-(valine-glycine).

20. Electroporation process according to any one of claims 1 to 16, characterized in that the peptide of molecular weight from 500 Da to 20 kDa is at least the epidermal growth factor EGF of sequence SEQ ID No.

1.

21. Electroporation process according to any one of the preceding claims, characterized in that the composition comprises at least one peptide of molecular weight from 500 Da to 20 kDa, and in particular at least one N-acylamino-amide elastase inhibitor compound, in a content of between 0.2% and 10%, preferably between 0.5% and 5%, and more particularly between 0.8% and 2% by weight, relative to the total weight of the composition.

22. An electroporation process according to any one of the preceding claims, characterized in that the composition comprises 1 wt% of at least one peptide with a molecular weight ranging from 500 Da to 20 kDa, in particular at least one inhibitory N-acylaminoamide compound elastases, and in particular N-acety 1-3-trifluoromethyl 1-pheny 1- (valine-glycine).

23. Electroporation process according to any one of the preceding claims, characterized in that the composition has a water content of between 20% and 100% by weight, in particular between 40% and 95% by weight, and preferably between 60% and 90% by weight, relative to the total weight of the composition.

24. Electroporation process according to any one of the preceding claims, characterized in that the composition comprises at least one alcohol, selected in particular from polyols, especially selected from glycols.

25. Electroporation process according to any one of the preceding claims, characterized in that the composition comprises a thickener / gelling agent.

26. Electroporation process according to any one of the preceding claims, characterized in that the composition is of the gel type, or is an oil-in-water emulsion.

27. ​​Electroporation process according to any one of the preceding claims, characterized in that the composition has a pH ranging from 2 to 7.5, preferably from 3 to 6, and more preferably from 3 to 5.

28. A kit for carrying out the process according to any one of the preceding claims, comprising: - an electroporation device having at least one electrode (2) and at least one counter electrode (3) and arranged to subject the keratinous materials to a succession of pulses of an electric current, each pulse having a duration (tpUke) of between 1 ms and 5 s, with a rest interval (Toff) between them of between 0.1 s and 5 s, and the electric current having a voltage amplitude of between 20 V and 400 V, preferably between 25 V and 300 V, even better between 30 V and 200 V, and an intensity of between 0.1 mA and 10 mA, and - a composition comprising at least one peptide with a molecular weight of between 500 Da and 20 kDa, in particular at least one N-acylaminoamide inhibitor of elastases, in particular at least of N-acety 1-3-trifluoromethyl 1-pheny 1- (valine-glycine).

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