WO2023242526A1

WO2023242526A1 - Iontophoretic method for administering ferulic acid

Info

Publication number: WO2023242526A1
Application number: PCT/FR2023/050905
Authority: WO
Inventors: Oana HULEA; Guillaume PELUCHON; Clélia THIERRY
Original assignee: Feeligreen
Priority date: 2022-06-17
Filing date: 2023-06-19
Publication date: 2023-12-21
Also published as: FR3136677A1

Abstract

The invention relates to an iontophoretic cosmetic and non-therapeutic method for delivering ferulic acid through the skin, a cosmetic composition suitable for an iontophoretic method comprising ferulic acid and an iontophoretic kit comprising said composition.

Description

Iontophoretic method of administering ferulic acid

TECHNICAL FIELD OF THE INVENTION

The present invention relates to the field of skin care.

Iontophoresis is an active technique which improves the passage of certain molecules into or through the skin using a low electric current (< 1 mA). An iontophoretic device consists of a power source and at least two electrodes. One electrode is active, as the current entry point, the other is passive, as the current exit point. One electrode is then the anode, preferentially connected to the positive pole, while the other is the cathode, preferentially connected to the negative pole. The main mechanisms of iontophoresis are:

• Electro-migration or electro-repulsion: the electric current causes the ions to migrate according to their charge. A positively charged molecule in a formulation placed under the anode(+) will be repelled towards the skin and will be attracted to the electrode(-). On the contrary, a negatively charged molecule in a formulation placed under the cathode (-) will be repelled towards the skin and will be attracted by the electrode (+);

• Electro-osmosis or convective transport: allows the transport of molecules thanks to the movements of the solvent from the anode towards the skin and from the skin towards the cathode. This flow is possible thanks to the negative charges of the skin at physiological pH.

Many active molecules in skin care compositions are in ionic form, therefore iontophoresis can be an effective tool for the delivery of these active molecules.

Analysis of penetration profiles in the skin suggests insufficient penetration of ferulic acid by simple topical application.

It is necessary to increase the penetrated quantity and release kinetics of ferulic acid and improve the release rate into the skin, compared to topical application.

It was surprisingly discovered that the pH of the cosmetic composition is crucial for improving the penetration of ferulic acid into the skin by iontophoresis. SUMMARY OF THE INVENTION

A first subject of the invention relates to a cosmetic and non-therapeutic iontophoretic process for delivering ferulic acid through the skin, comprising the following steps:

• Apply to the skin a composition comprising ferulic acid and one or more cosmetically acceptable additives, the pH of said composition ranging from 5.0 to 6.5, preferably from 5.0 to 6.0, and so still preferred from 5.4 to 5.6;

• Apply simultaneously, successively or sequentially over a certain time range a direct current, discontinuous current or a combination of the two from a device comprising at least one electrode applied to the skin, so as to improve the transport of ferulic acid through the skin.

A second object of the invention relates to a cosmetic composition suitable for an iontophoretic process comprising ferulic acid and one or more cosmetically acceptable additives, the pH of said composition ranging from 5.0 to 6.5, preferably 5. 0 to 6.0, and more preferably from 5.4 to 5.6.

A third object of the invention relates to an iontophoretic kit comprising:

- a cosmetic composition suitable for an iontophoretic process comprising ferulic acid and one or more cosmetically acceptable additives, the pH of said composition ranging from 5.0 to 6.5, preferably from 5.0 to 6.0, and more preferably from 5.4 to 5.6, and

- an iontophoretic device for implementing the process according to the invention.

FIGURES

[Fig. 1]: diagram of an iontophoresis device according to one embodiment

[Fig. 2]: diagram of an iontophoresis device according to another embodiment

[Fig. 3]: discontinuous current density waveform for iontophoresis

[Fig. 4]: diagram of the principle of iontophoretic transport

[Fig. 5]: photograph of the flexible electrodes

[Fig. 6]: photograph of the assembly

[Fig. 7]: annotated photograph of the comparison montage of the broadcast

[Fig. 8]: comparison diagram of the cutaneous diffusion of ferulic acid contained in serum by iontophoresis

[Fig. 9]: diagram of the percentage of ionization of ferulic acid as a function of pH DETAILED DESCRIPTION OF THE INVENTION

Non-therapeutic cosmetic process

A first subject of the invention relates to a cosmetic and non-therapeutic iontophoretic process for delivering ferulic acid to the skin, comprising:

• Apply to the skin a composition comprising ferulic acid and one or more cosmetically acceptable additives, the pH of said composition ranging from 5.0 to 6.5, preferably from 5.0 to 6.0, and so still preferred 5.4 to 5.6;

The process which is the subject of the invention can use a composition comprising ferulic acid as defined below.

The method according to the invention can be applied to any biological subject, in particular mammals, preferably human beings.

Fluent

The current applied must not cause discomfort, risk of injury or side effects to the user. It is therefore necessary to ensure that the strength of the current and the shape of the electrical wave are bearable throughout the duration of the treatment. In certain cases, a discontinuous current can help avoid the risk of discomfort.

In certain embodiments of the iontophoresis process, the applied current is preferably continuous, with an average current density of 0.001 mA/cm ² to 0.5 mA/cm ² , preferably of 0.01 mA/cm ² to 0.4 mA/cm ² , and more preferably from 0.05 mA/cm ² to 0.3 mA/cm ² .

In certain embodiments of the iontophoresis process, the applied current is preferably discontinuous, with an average current density of 0.001 mA/cm ² to 0.5 mA/cm ² , preferably of 0.01 mA/cm ² to 0.4 mA/cm ² , more preferably 0.05 mA/cm ² to 0.3 mA/cm ² and particularly preferably 0.13 mA/cm ² to 0.45 mA/cm ² . In certain embodiments of the iontophoresis process, the applied current is discontinuous with an average current density of 0.001 mA/cm ² to 0.5 mA/cm ² , preferably 0.01 mA/cm ² to 0, 4 mA/cm ² , and more preferably from 0.05 mA/cm ² to 0.3 mA/cm ² .

Preferably, the average intensity of the current is between 0.001 mA and 0.5 mA and is for example of the order of 0.1 mA.

In some embodiments of the iontophoresis method, direct current and discontinuous current are applied in combination, preferably with the above current densities.

“Discontinuous current” or “pulsed current” means a current whose intensity varies over time.

By direct current we mean a current whose intensity does not vary over time, that is to say that the intensity is constant and is independent of time.

In some embodiments of the iontophoresis method, the applied discontinuous current has sinusoidal waveforms, non-sinusoidal waveforms, or combinations thereof.

In some embodiments of the iontophoresis method, the discontinuous current applied has periodic square waveforms, rectangular waveforms, sawtooth waveforms, spike waveforms, trapezoidal waveforms, triangular waveforms, or combinations thereof.

Preferably, the discontinuous current applied has rectangular waveforms, advantageously with an average intensity of 0.001 mA/cm ² to 0.5 mA/cm ² , preferably of 0.01 mA/cm ² to 0.4 mA/ cm ² , and more preferably from 0.05 mA/cm ² to 0.3 mA/cm ² .

In some embodiments of the iontophoresis method, the current is applied for 30 seconds to 120 minutes, preferably 2 minutes to 50 minutes and more preferably 3 minutes to 40 minutes. In some embodiments, the direct current stimulus may be applied for a duration of 2, 5, 10 or 20 minutes.

Figure 3 illustrates an embodiment of representative current density waveform electrical stimuli generated by the circuitry of the iontophoresis device.

Referring to Figure 3, a first current density waveform is illustrated for iontophoresis. Figure 3 illustrates an embodiment of a waveform that can be generated by the circuit and the iontophoresis device of Figure 1 or 2.

Figure 3 illustrates a discontinuous current waveform stimulus having a rectangular wave profile. The average intensity of this current is of the order of 0.1 mA. The maximum intensity of this current is around 0.2 mA. Each 0.2 mA current pulse is applied for approximately 40 ms, then no current is applied for another 40 ms period, and so on. The current frequency is around 12.5 Hz.

The current density and duration values illustrated in Figure 3 are given as an example and are not limiting.

Cosmetic composition suitable for iontophoresis

A second subject of the invention relates to a cosmetic composition suitable for an iontophoretic process comprising ferulic acid and one or more cosmetically acceptable additives, the pH of said composition ranging from 5.0 to 6.5, preferably 5. 0 to 6.0, and more preferably from 5.4 to 5.6.

By “cosmetic composition adapted to an iontophoretic process”, it is meant that the active principle included in the composition, in this case ferulic acid, is in a sufficiently ionized form, so that the application of a current on the skin to which the composition is applied allows the electromigration of ferulic acid, in other words the transport of ferulic acid through the skin.

By “sufficiently ionized” is meant that the percentage of ionization of the ferulic acid within the composition is typically at least 80%, preferably at least 90%. The ionization percentage depends mainly on the pH of the composition. It can be calculated using the following Henderson-Hasselbach equation:

in which [A] and [AH] represent the respective concentrations of the conjugated base and acid forms of ferulic acid.

Assets

Ferulic acid is an organic acid found in certain plants, such as wheat, white willow and Roman chamomile. It is obtained from the hydrolyzation and refining of natural ferulic acid esterase. It is also biosynthesized in plants from caffeic acid under the action of the enzyme caffeate-O-methyltransferase.

Ferulic acid has the formula:

Its pKa is 4.58 and its molecular weight is 194 Da.

Due to these physicochemical properties (water-soluble and ionizable molecule at a pH between 4 and 6.5) ferulic acid is a good candidate for iontophoresis.

In a formula with a pH between 5 and 6.5, ferulic acid is sufficiently ionized, that is to say negatively charged, and is therefore compatible with the electro-migration mechanism (main mechanism of iontophoresis ).

The charged active ingredient (-) will be repelled by the electrode (-) to penetrate the skin in greater quantities compared to passive diffusion.

The pH of the composition is therefore greater than the pKa of ferulic acid. The composition has a pH varying from 5 to 6.5, preferably from 5 to 6, even more preferably from 5.4 to 5.6, so that the composition is both suitable for an iontophoretic process and compatible for application to the skin. The pH of the composition can be adjusted by adding a base or acid according to any methods known to those skilled in the art, for example by adding sodium hydroxide.

At a pH below 5, the ionization percentage of ferulic acid in water is less than 72%. In a pH range from 5 to 6.5, the ionization percentage of mandelic acid in water varies from 72% to 99% respectively. In particular, in a pH range going from 5 to 6, the percentage of ionization of ferulic acid in water changes respectively from 72% to 96%, and in a pH range going from 5.4 to 5 ,6, the ionization percentage of mandelic acid in water changes respectively from 87% to 91.

Advantageously, the composition comprises from 0.001 to 10.0% by weight, preferably 0.1 to 4.0% by weight, and more preferably from 0.5 and 1.0% by weight of ferulic acid relative to to the total weight of the composition.

The amount of ferulic acid in the composition influences the pH of the composition. Indeed, ferulic acid, by definition, acidifies the composition and will therefore reduce its pH. Advantageously, the composition comprises a quantity of ferulic acid less than or equal to 10% by weight relative to the total weight of the composition, preferably a quantity of ferulic acid between 0.1 and 4% by weight, so as to maintain a pH ranging from 5 to 6.5, more particularly from 5 to 6, without the need to add an acid or a base to adjust the pH.

Additives

The composition may further comprise one or more polar solvent(s) compatible for application to the skin, preferably present in an amount of at least 30% by weight, preferably in an amount of at least 40% by weight, and more preferably in an amount of at least 50% by weight, relative to the total weight of the composition. The polar solvent(s) are for example chosen from water and alcohols, such as ethanol.

The composition may further comprise one or more anionic or nonionic polymers present in quantities ranging from 0.01% to 30% by weight, preferably from 0.1% to 10% by weight, relative to the total weight of the composition. . The anionic polymer(s) are for example chosen from nucleic acid derivatives, proteins, polypeptides and polysaccharides, such as polyglutamate, alginate, pectin or hyaluronic acid.

The composition may further comprise one or more gum(s) chosen from the group consisting of xanthan gum, Caesalpinia spinosa gum (tara or carob gum from Peru) and Sclerotium rolfssii gum.

Advantageously, the composition comprises 0.3 to 3.0% by weight, preferably 0.4 to 2.0% by weight, preferably 0.4 to 1.5% by weight and more preferably 0 .5 to 1.0% by weight of Caesalpinia spinosa gum (tara gum or Peruvian carob) relative to the total weight of the composition. Advantageously, the composition comprises at most 0.6% by weight of Caesalpinia spinosa gum (tara gum or Peruvian carob) relative to the total weight of the composition.

Advantageously, the composition comprises from 0.1 to 1.3% by weight, preferably from 0.2 to 1.1% by weight, preferably from 0.3 to 0.9% by weight and preferably from 0. .3 to 0.8% by weight of the gum of Sclerotium rolfssii relative to the total weight of the composition. Advantageously, the composition comprises a maximum quantity of Sclerotium rolfssii gum and Caesalpinia spinosa gum less than or equal to 1.0% by weight relative to the total weight of the composition.

Advantageously, the composition comprises a ratio of Caesalpinia spinosa gum (tara gum or Peruvian locust bean): Sclerotium rolfssii gum by weight ranging from 1:5 to 5:1, preferably from 1:2 to 2:1.

In a preferred embodiment, the composition comprises:

- from 0.5 to 1.0% by weight of Caesalpinia spinosa gum (tara gum or Peruvian carob) relative to the total weight of the composition and for example 0.6% by weight;

- from 0.3 to 0.8% by weight relative to the total weight of the composition of the gum of Sclerotium rolfssii and for example 0.3% by weight; in which the sum of the proportions of Caesalpinia spinosa gums and Sclerotium rolfssii is at most 1.0% by weight relative to the total weight of the composition.

A composition according to this embodiment advantageously has excellent stability. The composition may comprise water present in an amount of at least 30% by weight, in particular in an amount of at least 60% by weight, and more preferably in an amount of at least 80% by weight, relative to the total weight of the composition.

The composition is, for example, free of any ionizable preservative.

The composition may further comprise one or more texturizing agents chosen from the group consisting of Glucomannan, cellulose derivatives such as Hydroxypropyl Methylcellulose, gums such as xanthan.

In known manner, the dosage forms dedicated to topical administration can also contain conventional adjuvants in the cosmetic and/or dermatological field.

The composition may further comprise one or more selected multi-functional ingredients selected from the group consisting of, non-ionic Pentylene glycol, 1,2 hexanediol, Gaprylyl glycol, Propanediol and O-Cymen-5-ol. These ingredients, generally at a concentration of no more than 15% by weight relative to the total weight of the composition, make it possible to reinforce the antimicrobial properties of the final product.

Galenic

Such a composition may be in the form of an aqueous, hydroalcoholic solution, a solution or dispersion of lotion or serum type, an emulsion of liquid or semi-liquid consistency of milk type, obtained by dispersing a fatty phase in an aqueous phase (OÀV) or vice versa (W/O), or a suspension, or emulsion, of soft, semi-solid or solid consistency, of the cream, aqueous or anhydrous gel type, a microemulsion, a microcapsule, a microparticle, or a vesicular dispersion of ionic and/or non-ionic type.

These compositions are prepared according to the usual methods known to those skilled in the art.

Route of administration

A composition according to the invention is advantageously administered topically to the skin. It can be used for cosmetic and/or dermatological treatment of the skin.

Iontophoresis kit

The invention also relates to an iontophoresis kit comprising:

• Cosmetic composition suitable for an iontophoretic process comprising ferulic acid and one or more cosmetically acceptable additives, the pH of said composition ranging from 5.0 to 6.5, preferably from 5.0 to 6.0, and from still preferred way from 5.4 to 5.6, and

• An iontophoretic device to implement the process as described above.

The iontophoresis composition may be as described above.

The selected current profile may be as described above in relation to the method.

In certain embodiments, the kit according to the invention is in the form of a tube (or container) comprising the cosmetic composition according to the invention and an electronic cap comprising said iontophoretic device to implement the method as described above.

Iontophoretic device

With reference to Figure 1, an iontophoresis device 1 and a set of electrodes 41, 42, 43 are illustrated schematically. In this embodiment, the iontophoresis device 1 comprises an electronic plug 4 advantageously connected to a tube 2, containing a cosmetic composition, in particular such as that described above. The electronic plug 4 is preferably assembled on the tube 2 in a reversible manner, in particular by screwing. This allows the user to easily change the tube 2, and therefore to change composition and cosmetic treatment, while retaining a single electronic cap 4. For example, the user could thus have in his possession a single cap electronic 4 and different tubes 2, for example a first tube with the ferulic acid composition defined previously, a second tube with another composition suitable for iontophoretic use, etc. It will then be possible and easy for the user to alternate between the different cosmetic compositions in order to benefit from different cosmetic treatments on the skin. By electronic plug 4 is meant any electronic and/or electrical and/or electromechanical device capable of generating a current, in particular a current such as that described previously and illustrated in Figure 3. The electronic plug 4 is designed to be placed in contact of the user's skin during treatment, in particular via the electrodes 41, 42, 43. Preferably, the electronic cap 4 is designed to be mounted reversibly, in particular by screwing, on the tube 2 containing the composition cosmetic.

According to another embodiment of the iontophoretic device 1 illustrated in Figure 2, the device further comprises a cannula 3, disposed between the electronic plug 4 and the tube 2. This cannula 3 is designed to, on the one hand, be mounted on the tube 2 preferably in a reversible manner, for example by screwing, and on the other hand, pass through the electronic plug 4, as can be seen in Figure 2. The cannula 3 can be designed to cooperate with the electronic plug according to the principle of a pivot connection. This cannula 3 then makes it possible to convey the cosmetic composition from tube 2 to the user's skin without coming into contact with the electronic cap 4, thus preserving the electronic components of the latter, improving hygiene and facilitating cleaning. of the last.

According to one embodiment, the iontophoretic device 1 is produced in accordance with that described in the patent application filed by the applicant under the filing number FR2200962.

Whatever the embodiment of the iontophoretic device 1, the electronic plug 4 notably comprises a power source (not shown), such as a cell or a rechargeable battery, a current waveform generator (not shown). ), a first electrode (active) 41, a second electrode (counter or return) 42. The device can also include other electrodes and other elements (such as a light-emitting diode for example) without departing from the scope of the invention .

In the illustrated embodiments, the electronic cap also includes an orifice 44 designed to deliver the cosmetic composition to the user's skin, in particular following the pressure that the user will exert on the tube 2 during the treatment.

In the embodiment where the electronic plug 2 comprises a cannula 3 (Figure 2), the latter is connected in a sealed manner to the orifice 44, so that the composition cosmetic contained in the tube 2 is delivered directly to the skin of the user, passing through the electronic cap 2 without however coming into contact with the internal components (in particular electronic and/or electrical) of the latter.

The objective of Figures 1 and 2 is to illustrate and describe some of the main functional components of an iontophoresis device used to carry out one or more of the various embodiments of the methods described herein.

The circuits used to perform the functions of the iontophoresis device are implicit, inherent and well known to those skilled in the art so that they will not be described in further detail here.

In certain embodiments, the iontophoresis device is packaged in the form of a manual device which can be carried in one hand during treatment, as is particularly the case with the embodiments illustrated in Figures 1 and 2 Treatment with a handheld device includes constantly moving the iontophoresis device over the skin such that at least the active electrode 41 is moved over the skin surface while making contact. Preferably it is the electronic cap 4 and tube 2 assembly, that is to say the entire iontophoretic device 1, which is moved by the user on his skin, as the iontophoretic treatment progresses. We could also imagine, without departing from the scope of the invention, that the iontophoretic device 1 is moved by a first user on the skin of a third party user, for example in the case of a cosmetic treatment carried out in a beauty institute. .

A suitable power source is any power source capable of generating electrical current to power the various other circuits and devices. In certain embodiments, a battery, preferably rechargeable, is used as a power source. In some embodiments, the iontophoresis device is plugged into a wall outlet. In some embodiments, the power source produces direct current.

In some embodiments, an iontophoresis device includes an iontophoresis patch model. By iontophoresis patch we mean any device intended to be applied to a specific area of the skin and to remain immobile there for at least a certain time so as to carry out localized and continuous iontophoresis treatment. So illustrative and non-limiting, the patch could be produced as that described in the applicant's patent published under the number FR 3 035 792 and/or FR 3 034 017.

In some embodiments, an iontophoresis device includes an iontophoresis face mask design. By facial mask we mean any device intended to be applied to a large area of the skin, such as the forehead and/or cheeks, around the eyes, the neck, and to remain immobile there for at least a certain time so as to to carry out a continuous iontophoresis treatment over the entire said area. By way of illustration and not limitation, the patch could be produced such as that described in the applicant's patent application published under number WO 2017/212343.

Cosmetic applications

In a preferred embodiment, the above method makes it possible to reduce spots on the hands and/or on the face and/or on the neck and/or décolleté, for example age spots and/or sun spots. and/or freckles and/or spots due to disease. Then, the above method allows depigmentation of the skin, especially in areas where the pigmentation is initially too high. After several uses or a single use of the method of the invention, the color of the skin is more uniform and its homogeneity is increased.

In another embodiment, the method is used to treat signs of aging, to improve skin smoothness, skin quality and appearance.

In another embodiment, the method is used to minimize signs of skin aging, and/or pigmentation, and/or volume, and/or sagging of wrinkles, and/or tone and/or wrinkles. spots, and/or to improve the firmness, and/or radiance, and/or smoothness of the skin. The method of the invention can be associated with the application of active agents associated with an electric current, in particular a microcurrent.

Ferulic acid is used in cosmetics for its antioxidant properties. It helps slow down premature skin aging caused by oxidative stress linked to multiple factors (diet, sun, tobacco, pollution, etc.).

Ferulic acid has strong antioxidant activity, it protects nerve cells but also skin cells from free radicals and external aggressions. Recent in vivo work has shed light on the deep mechanisms underlying anti-radical defenses as well as the positive action of ferulic acid. It acts on the Nrf2 protein, responsible for activating the skin's natural antioxidant defenses.

It also has a synergistic effect with other antioxidants such as vitamins C and E, reducing their breakdown.

This antioxidant activity provides the following cosmetic activities:

• Photoprotective: its antioxidant action is reinforced by exposure to UV, the active ingredient therefore constitutes protection against photoaging.

• Anti-radicals: fights against oxidative stress, particularly against “superoxides”, “hydroxyl radicals” and “nitrile oxide”. Reduces oxidative stress linked to diet, sun, tobacco, pollution...

• Anti-inflammatory and Soothing: soothes irradiation caused by UV by inhibiting the phosphorylation of casein Kinase 2.

• Anti-tyrosinase/Lightening: reduces melanin production in B16 cells.

• Anti-aging: increases the firmness of the skin and replenishes it, to reduce wrinkles.

EXAMPLES

1: acid solubility study

in 96% ethanol and

The solubility of ferulic acid is checked in different solvents (Ethanol 96% and butylene glycol) and at different concentrations (0.5 and 1.0% by weight) according to the following procedure.

We first weigh the percentage of ferulic acid to be evaluated in 20% of solvent. After adjusting the pH to 5.5 +/- 0.1 with sodium hydroxide, the mixture is placed under magnetic stirring at 500 rpm for 2 hours at room temperature (TA, 20° C +/- 2° C). If solubility is not achieved, stir again for 2 hours. Solubility is assessed visually (by observing the disappearance of the crystals). Results :

Example 2: study of solubility of ferulic acid (FA) in propanediol

The solubility of ferulic acid is checked at two concentrations (0.5% and 1% by weight) in propanediol (Zemea®) according to the following procedure.

We weigh the percentage of ferulic acid to be evaluated in 10% propanediol. The mixture is placed under magnetic stirring at 500 rpm for 2 hours at room temperature (RT). If solubility is not achieved, stir again for 2 hours.

Results :

Ferulic acid will be used at 0.5% mass for the remainder of the study.

Example 3: physicochemical study of ferulic acid

The pH influences several physicochemical parameters of ferulic acid: ionization, solubility and stability. (Figure 9)

pH 5.5 and 6.5 were selected for solubility/stability evaluation because they are compatible with the use of cosmetic products for the skin and cover a good part of the ionization range of ferulic acid.

Example 4: study of solubility of ferulic acid in a formulation

In order to evaluate the solubility of ferulic acid in the formula, the mixture of ferulic acid at 0.5% by weight from Example 2 is added to the formula described in Example 6 which will then be adjusted to the pH previously defined. The formulas are then stored at 4°C and room temperature. A visual reading is taken at T = 24 h.

Results :

When reading at T = 24 h, a recrystallization of ferulic acid is observed for the formulas at pH 3.5 and 4.5. At these pHs, the solubility of ferulic acid does not allow its use in formula. Stability monitoring of the formulas adjusted to pH 5.5 and 6.5 is carried out in order to confirm their relevance.

Example 5: stability study of formulas containing ferulic acid Following the solubility study, the formulas presenting good solubility are placed in stability at different temperatures in order to carry out accelerated aging tests under the following conditions.

Results :

The results after 15 days of stability show good stability of the formulas at 4°C and at TÀ for pH 5.5 and 6.5.

At 40°C, both formulas show color variation but are stable in other aspects.

At T1M, we note a slight change in the color of the formulas at TÀ. At 40°C, browning is observed for both formulas at this temperature, this phenomenon is nevertheless more intense and accompanied by deposits for the formula adjusted to pH 6.5. This suggests greater degradation of the active ingredient at pH 6.5.

Example 6: study of the iontophoretic effectiveness of ferulic acid

Material and method

1. Soft electrodes

Flexible electrodes (Àg/ÀgCl coated with carbon) are used as part of this study in static mode (see Figure 5). For viscous formulations, the deposits are applied directly to the electrodes using a mold.

For low viscosity formulations, the deposits are made on a non-woven support previously fixed on the electrodes using an adhesive film.

2. Diffusion cells

The diffusion cells comprise skin explants in a housing.

This study is carried out on porcine ear skin explants.

Porcine ear skin has the most similarities with human skin in terms of skin thickness, follicular structure, vascular anatomy and arrangement of collagen fibers.

The diffusion cells are placed in a water bath at 37°C to obtain a temperature of 32°C on the surface of the skin.

They are connected to a current generator (see Figure 6).

In this study, we compare diffusion with cells connected to electrodes (ÀD) to diffusion with unconnected cells (passive diffusion SD) (see Figure 7).

We thus calculate an improvement factor directly linked to iontophoresis which is equal to the average of the concentrations of the active ingredient in the skin for the ÀD samples divided by the average of the concentrations of the active ingredient in the skin for the SD samples. .

This report indicates the degree of improvement in the skin passage of the active ingredient by iontophoresis (ÀD) compared to passive application (SD). 3. Experimental conditions

4. Tested formula

Results

Figure 8 presents the comparison of the average areas of ferulic acid peaks measured at the cathode of cells with devices (ÀD -) compared to the average areas of ferulic acid peaks measured in control cells without devices (SD ).

The average of the ÀD - areas is 6.2 times greater than the average of the SD (control) areas. Consequently, iontophoresis makes it possible to very clearly improve the diffusion of ferulic acid compared to passive diffusion.

Example 7: study of the stability of a composition according to the invention

The stability of compositions according to the invention was evaluated at 4°C, at room temperature and at 40°C by observation of physicochemical characteristics (pH, viscosity, visual appearance) over time, at 0 days, 1 month and 3 months.

In particular, the compositions described in Examples 1 and 2 with 0.6% by weight of tara gum and 0.3% by weight of sclerotium rolfssii gum showed excellent stability after 3 months at the three temperatures tested.

Claims

1. Cosmetic and non-therapeutic iontophoretic process for delivering ferulic acid through the skin, comprising the following steps:

2. Method according to claim 1, in which a direct current is applied having an average current density of 0.001 mA/cm ² to 0.5 mA/cm ² , preferably of 0.01 mA/cm ² to 0.4 mA/cm ² , and more preferably from 0.05 mA/cm ² to 0.3 mA/cm ² .

3. Method according to claim 1, in which a discontinuous current is applied having an average current density of 0.001 mA/cm ² to 0.5 mA/cm ² , preferably of 0.01 mA/cm ² to 0.4 mA/cm ² , and more preferably from 0.05 mA/cm ² to 0.3 mA/cm ² .

4. Method according to claim 3, wherein a discontinuous current is applied having an average current density of 0.13 mA/cm ² to 0.45 mA/cm ² .

5. Method according to any one of the preceding claims, in which a current is applied for from 30 seconds to 120 minutes, preferably from 2 minutes to 50 minutes and even more preferably from 3 minutes to 40 minutes.

6. Method according to any one of the preceding claims, in which the composition comprises from 0.001 to 10.0% by weight, preferably from 0.1 to 4.0% by weight, and more preferably from 0.5 and 1.0% by weight of ferulic acid relative to the total weight of the composition.

7. Method according to any one of the preceding claims, said composition comprising one or more gum(s) chosen from the group consisting of xanthan gum, Caesalpinia spinosa gum (tara gum or Peruvian locust bean) and Sclerotium rolfssii gum.

8. Method according to claim 7, in which the composition comprises from 0.3 to 3.0% by weight, preferably 0.4 to 2.0% by weight, preferably from 0.4 to 1.5% by weight. weight and preferably from 0.5 to 1.0% by weight of Caesalpinia spinosa gum (tara gum or Peruvian carob) relative to the total weight of the composition.

9. Method according to claim 7 or 8, in which the composition comprises from 0.1 to 1.3% by weight of Sclerotium rolfssii gum relative to the total weight of the composition, preferably from 0.2 to 1.1 % by weight, preferably 0.3 to 0.9% by weight and preferably 0.3 to 0.8% by weight.

10. Method according to any one of claims 7 to 9, in which the composition comprises a ratio of Caesalpinia spinosa gum (tara gum or Peruvian carob): Sclerotium rolfssii gum by weight ranging from 1:5 to 5:1, of preferably 1:2 to 2:1.

11. Cosmetic composition suitable for an iontophoretic process comprising ferulic acid and one or more cosmetically acceptable additives, the pH of said composition ranging from 5.0 to 6.5, preferably from 5.0 to 6.0, and so still preferred from 5.4 to 5.6.

12. Cosmetic composition according to claim 11, comprising from 0.001 to 10.0% by weight, preferably 0.1 to 4.0% by weight, and more preferably from 0.5 to 1.0% by weight d ferulic acid relative to the total weight of the composition.

13. Cosmetic composition according to claim 11 or 12, comprising one or more gum(s) chosen from the group consisting of xanthan gum, Caesalpinia spinosa gum (tara gum or Peruvian locust bean) and Sclerotium rolfssii gum .

14. Cosmetic composition according to claim 13, comprising from 0.3 to 3.0% by weight, preferably 0.4 to 2.0% by weight, preferably from 0.4 to 1.5% by weight and preferably from 0.5 to 1.0% by weight of Caesalpinia spinosa gum (tara gum or Peruvian carob) relative to the total weight of the composition.

15. Composition according to claim 13 or 14, comprising from 0.1 to 1.3% by weight of Sclerotium rolfssii gum relative to the total weight of the composition, preferably from 0.2 to 1.1% by weight, preferably from 0.3 to 0.9% by weight and preferably from 0.3 to 0.8% by weight.

16. Composition according to any one of claims 13 to 15, said composition comprising a ratio of Caesalpinia spinosa gum (tara gum or Peruvian carob): Sclerotium rolfssii gum by weight ranging from 1:5 to 5:1, preferably from 1:2 to 2:1.

17. Iontophoretic kit comprising:

Cosmetic composition suitable for an iontophoretic process comprising ferulic acid and one or more cosmetically acceptable additives, the pH of said composition ranging from 5.0 to 6.5, preferably from 5.0 to 6.0, and so still preferred from 5.4 to 5.6, and

An iontophoretic device for implementing the method according to any one of claims 1 to 10.

18. Kit according to claim 17, in the form of a tube comprising a container comprising said cosmetic composition and a cap comprising said iontophoretic device for implementing the method according to any one of claims 1 to 10.