HK1176949B - Novel caspase-14 activator peptides and compositions comprising the same - Google Patents

Description

Novel caspase-14 activating peptides and compositions comprising the same

Technical Field

The present invention relates to the field of cosmetics and pharmaceuticals. The present invention relates to peptide compounds of the following general formula (I) as caspase-14 activators: r₁–(AA)_n–X₁–X₂–Ile–Gln–Ala–Cys–Arg–Gly–X₃–(AA)_p–R₂And toTheir use in cosmetics and/or pharmaceuticals for preventing and/or correcting DNA damage, preventing and/or treating the signs of skin aging and photoaging, and improving skin barrier function.

Background

The primary function of the largest organ skin in the human body is to protect the body from many forms of insult, including external insults. Examples of such insults include such insults as soiling, UV radiation, or irritating chemicals such as surfactants, preservatives or fragrances, and mechanical insults such as scratching, shaving or depilation. Contamination means "external" contamination, for example due to diesel particles, ozone or heavy metals, and "internal" contamination, which may be due in particular to solvents released by paints, glues or wallpaper (for example toluene, styrene, xylene or benzaldehyde), or also to cigarette smoke. Air drying is also a major cause of skin damage. Such external aggressions cause a change in the barrier function of the skin, which leads to discomfort of the skin, unpleasant sensory phenomena such as tightness or itching, or even excessive fragility and redness. Furthermore, these external aggressions promote the acceleration of the so-called "extrinsic" ageing of the skin. In fact, exogenous aging is caused by environmental factors that the body experiences throughout its life, collectively referred to as external aggressions.

In addition to its role as a physical barrier, skin also functions as a water-impermeable barrier to prevent dehydration. This barrier formed by the skin consists of several layers, containing different types of cells that ensure the skin to be constantly renewed. First, this renewal process involves a phenomenon in which the superficial cells of the skin are shed, which must be compensated by epidermal renewal ensured by keratinocytes in the basal layer, which actively divide and differentiate into cells of the stratum corneum or keratinocytes (corneocytes). The skin repair effects in these rejuvenation and damage (e.g., UV-radiation induced damage) situations are highly controlled by a set of signaling pathways. One of these signaling pathways includes the protease caspase-14. Caspase-14 is a unique member of the caspase family. Indeed, unlike other members of the widely expressed caspase family, caspase-14 is only expressed and active in the epidermis and is absent in most other adult tissues (eckhartetal, j. invest. dermaltol., 2003,44: 1148-. The important role of caspase-14 in the formation of a barrier consisting of the epidermis has recently been demonstrated (deneckeret al, nat. cell. biol.2007,9: 666-. In fact, it is expressed and exerts its proteolytic action only in those epidermal layers which are differentiated and "cornified" and in the hair follicles (Lippenstal, CellDeathDiffer, 2000,10: 257-. However, caspase-14 has been shown to play an important role, especially in the maintenance of the hydration process, keratinocyte formation and apoptosis protection, especially in the case of external insults, such as those due to UV radiation (deneckeret al, j.cell biology,2008, 451-. In addition, caspase-14 is shown to be responsible for cleaving profilaggrin (profilaggrin) into filaggrin, which is then hydrolyzed into peptides and amino acids, which form natural moisturizing factors (hosteetal, j.invest.dermatol.abstract,2007, S71). All these conclusions lead to the development of pharmaceutical compositions comprising caspase-14 as active ingredient, which can be used as sunscreens (WO 2008025830). However, there is currently no cosmetic compound available that allows the use of caspase-14, thereby converting filaggrin into filaggrin to be activated to protect the skin from UV radiation and improve barrier function, although there is indeed a need for new care of this type.

Disclosure of Invention

Now, the applicant has demonstrated that the peptide compounds of general formula (I) below are excellent activators of caspase-14 and have a significant effect on improving the skin barrier function and protecting the skin from external aggressions such as UV radiation (in particular DNA protection function):

R₁–(AA)_n-X₁–X₂–Ile–Gln–Ala–Cys–Arg–Gly–X₃–(AA)_p-R₂。

the peptide compounds of the invention are characterized in that they

-activation of caspase-14 and thus its proteolytic action on filaggrin;

help maintain hydration of the epidermis;

-preventing and repairing DNA damage of skin cells subjected to UVB radiation; and

-optimizing the barrier function of the epidermis.

Accordingly, a first object of the present invention is to provide a peptide compound of the following general formula (I):

R₁-(AA)_nX₁-X₂-Ile-Gln-Ala-Cys-Arg-Gly-X₃-(AA)_p-R₂。

it is a second object of the present invention to provide a cosmetic composition comprising the peptide compound of formula (I) as a main active ingredient.

Furthermore, a third object of the present invention relates to the use of a cosmetic composition comprising said peptide compound of formula (I) for (I) protecting and/or repairing DNA damage, activating caspase-14 and filaggrin formation, (ii) preventing and/or treating the signs of skin aging and photoaging, and (iii) improving skin barrier function and epidermal hydration.

Finally, a fourth object of the present invention is to provide a method for the cosmetic treatment of the skin or keratinous appendages to be treated, using a composition comprising said peptide compound of formula (I).

A first object of the present invention relates to peptide compounds of general formula (I):

R₁–(AA)_n-X₁–X₂–Ile–Gln–Ala–Cys–Arg–Gly–X₃–(AA)_p–R₂

(I)

wherein

X₁Aspartic acid, glutamic acid or no amino acid;

X₂asparagine, proline, serine or no amino acid;

X₃asparagine, arginine, leucine or no amino acid;

AA is any amino acid, and n and p are integers from 0 to 2;

R₁is a primary amine function of a free N-terminal amino acid, R₂A hydroxyl group which is a carboxyl function of the C-terminal amino acid, which may be selected from C₁-C₃₀Alkyl chain substituted by a group, or NH2, NHY or NYY, wherein Y is C₁-C₄An alkyl chain;

the sequence of formula (I) comprises 6-13 amino acid residues.

The term "peptidal compound" or "peptide" denotes a chain of two or more amino acids linked together by peptide bonds or modified peptide bonds.

"peptidal compound" or "peptide" means a naturally occurring or synthetic peptide of the invention as described above, or at least one of its fragments obtained by proteolysis or synthesis, or any naturally occurring or synthetic peptide whose sequence consists wholly or partly of the above-mentioned peptide sequence.

The amino acids constituting the peptide compounds of the present invention may be in the levorotatory configuration, i.e., the L-configuration, and/or may be in the dextrorotatory configuration, i.e., the D-configuration. The peptides of the invention may thus be in the L-, D-or DL-form.

In order to improve resistance to degradation, it may be necessary to use protected forms of the peptides of the invention. The protective form must obviously be a biologically compatible form and should be compatible with the cosmetic and pharmaceutical fieldsThe applications in (1) are compatible. Preferably, for protection of the primary amine function of the N-terminal amino acid, a compound having C₁-C₃₀Acyl-type substituent R of saturated or unsaturated alkyl chain₁The substituents may be selected from acetyl or aromatic groups. Preferably, to protect the carboxyl function of the C-terminal amino acid, C is used₁-C₃₀Alkyl chain type substituent group R₂Or R is₂Is a NH2, NHY or NYY group wherein Y is C₁-C₄An alkyl chain.

The peptides of the invention may be protected at the N-terminus, the C-terminus, or both.

In a first preferred embodiment of the present invention, in the general formula (I),

X₁aspartic acid, glutamic acid or no amino acid;

X₂asparagine, proline, serine or no amino acid;

X₃asparagine, arginine, leucine or no amino acid;

the integers n and p are equal to 0;

R₁primary amino function being a free N-terminal amino acid, R₂A hydroxyl group which is a carboxyl function of the C-terminal amino acid, which may be selected from C₁-C₃₀Alkyl chain substituted by a group, or NH2, NHY or NYY, wherein Y is C₁-C₄An alkyl chain;

the sequence of formula (I) comprises 6-9 amino acid residues.

In a second preferred embodiment, the peptide compound corresponds to one of the following formulae:

(SEQIDNo:1)Asp–Pro–Ile–Gln–Ala–Cys–Arg–Gly–NH₂

(SEQIDNo:2)Ile–Gln–Ala–Cys–Arg–Gly–NH₂

(SEQIDNo:3)Asn–Arg–Ile–Gln–Ala–Cys–Arg–Gly-NH₂

(SEQIDNo:4)Pro-Ile-Gln-Ala-Cys-Arg-Gly-Phe-NH₂

the invention also relates to homologous forms of these sequences. According to the invention, "homologous" means any peptide sequence which is at least 50%, or preferably at least 80% and more preferably at least 90% identical to a peptide sequence selected from the sequences SEQ ID No. 1 to SEQ ID No. 4. "peptide sequences that are at least X% identical" means the percentage of similarity between the amino acid residues of two sequences being compared, obtained after optimal alignment of the two sequences. The best alignment is obtained using local homology algorithms, such as those used in the BLASTP computer software available from the NCBI website.

The term "homologous" may also refer to peptides which differ from the peptide sequence of SEQ ID No. 1 to SEQ ID No. 5 by virtue of a substitution of a chemically equivalent amino acid, i.e. by virtue of a substitution of one residue with another residue having the same characteristics. Conventional substitutions are therefore made between Ala, Val, Leu and Ile; between Ser and Thr; between the acidic residues Asp and Glu; between Asn and Gln; and between the basic residues Lys and Arg; or between the aromatic residues Phe and Tyr.

The peptides of general formula (I) of the invention can be obtained from their constituent amino acids or derivatives by conventional chemical synthesis (in solid or liquid homogeneous phase) or by enzymatic synthesis (Kullmanet, J.biol.chem.1980,225, 8234).

The peptides of the invention may be naturally occurring or synthetic. Preferably, according to the invention, the peptide is obtained by chemical synthesis.

Finally, the active ingredient may be a single peptide, a mixture of peptides or peptide derivatives and/or consist of amino acid derivatives.

The peptide compounds of the invention can be used as medicaments.

According to an advantageous embodiment of the invention, the peptide compounds according to the invention are dissolved in one or more physiologically suitable solvents conventionally used by those skilled in the art, such as water, glycerol, ethanol, propylene glycol, butylene glycol, dipropylene glycol, ethoxylated or propoxylated diethylene glycol, cyclic polyols or any mixtures of these solvents.

According to another advantageous embodiment of the invention, the peptide compounds of the invention are dissolved in cosmetic or pharmaceutical carriers, such as liposomes, or adsorbed on powdered organic polymers, mineral supports, such as talc and bentonite, more generally dissolved or fixed to any physiologically suitable carrier.

The second object of the present invention relates to a cosmetic composition comprising the peptide compound of the general formula (I) as an active ingredient. Preferably, the composition of the invention is in a form suitable for topical application, comprising a cosmetically acceptable medium. By "cosmetically acceptable" is meant a medium suitable for contact with the skin or human keratinous appendages without any risk of toxicity, incompatibility, instability, allergic response, and the like. The compositions for application to the skin may be in the form of creams, oil-in-water or water-in-oil emulsions or multiple emulsions, solutions, suspensions, microemulsions, aqueous or anhydrous gels, essences (serum), or may also be in the form of vesicle dispersions, patches, sprays, ointments, creams, emulsions, colloids, milks (mils), lotions, lipsticks, or may also be powders, all suitable for application to the skin, lips, and/or keratinous appendages.

Preferably, the peptide compound is present in the composition at a concentration of about 0.0005 to 500ppm, preferably 0.01 to 5 ppm.

More preferably, the composition of the invention further comprises at least one other active ingredient, which promotes the action of the peptide compound. Examples include, but are not limited to, the following classes of ingredients: other active peptide substances, plant extracts, healing, anti-ageing, anti-wrinkle, sedative (soothing), radical scavengers and anti-UV substances, substances stimulating dermal macromolecule synthesis or energy metabolism, hydrating, antibacterial, antifungal, anti-inflammatory substances, anesthetics, substances regulating skin differentiation, pigmentation or depigmentation, substances stimulating nail or hair growth, etc. Preferably, substances with anti-wrinkle activity such as radical scavengers or antioxidants, or substances that stimulate the synthesis of dermal macromolecules, or substances that stimulate energy metabolism are used. In particular, the active ingredient is selected from vitamins, phytosterols, flavonoids, DHEA and/or its precursors or chemical or biological derivatives thereof, metalloproteinase inhibitors or retinoids. In addition, additives such as solvents, diluents, dyes, sunscreens, self-tanning agents, pigments, fillers, preservatives, odor absorbers, thickeners, emulsifiers, humectants, emollients, fragrances, antioxidants, film formers, chelating agents, masking agents, conditioning agents, and the like may be added to the composition.

In all cases, the person skilled in the art will ensure that these adjuvants and their proportions are chosen so as not to impair the advantageous properties of the compositions of the invention. For example, these adjuvants may be present in an amount of 0.01 to 20% by weight of the total composition. When the composition of the invention is an emulsion, the fatty phase may represent from 5 to 80% by weight, and preferably from 5 to 50% by weight, of the total weight of the composition. The emulsifiers and co-emulsifiers used in the composition are selected from those conventionally used in the art. These emulsifiers and co-emulsifiers may be used, for example, in amounts of from 0.3 to 30% by weight, based on the total weight of the composition.

A third object of the present invention relates to the use of a composition comprising the peptide compound of the present invention for preventing and/or repairing DNA damage, activating caspase-14 and forming filaggrin. A peptide compound intended to "prevent and/or repair DNA damage" means a biologically active peptide compound or derivative capable of repairing damage due to photochemical reactions between DNA bases (e.g., the formation of cyclobutane pyrimidine dimers). By a peptide compound "enabling caspase-14 activation" is meant any biologically active peptide or derivative capable of increasing the amount of caspase-14, either by increasing the protein synthesis of caspase-14 (by direct or indirect regulation of gene expression), or by other biological processes, such as the stabilization or destabilization of messenger RNA transcripts. A peptide compound that results in an increase in "formation of filaggrin" means any biologically active peptide or derivative that is capable of increasing the amount of filaggrin that is converted to filaggrin, either by an increase in the proteolytic activity of caspase-14, or by an increase in the amount of caspase-14.

In particular, the compositions of the present invention are used to prevent and/or repair DNA damage caused by external insults. "external aggression" refers to an aggression that can be caused by the environment. Examples include such insults as soiling, UV radiation, or irritating chemicals such as surfactants, preservatives or fragrances, mechanical insults such as scratching, shaving or depilation. Preferably, however, the external aggression is mainly UV radiation, in particular UVB radiation.

Another object of the present invention relates to the use of a cosmetic composition comprising said peptide compound and a cosmetically acceptable medium for preventing and/or treating the signs of skin aging and photoaging. "signs of skin aging" include, but are not limited to, all the obvious manifestations caused by skin aging. Specifically, this refers to wrinkles, deep and coarse wrinkles, fine lines, cracks, sagging skin and subcutaneous tissue, loss of skin elasticity, and stiffness (stringiness), loss of firmness and tone, and dermal atrophy. Furthermore, "signs of skin aging" also indicate enlarged pores, blemishes, discoloration, age spots, keratosis, collagen loss, and other changes in the dermis and epidermis, but also any change in the appearance of the skin and keratinous appendages due to aging, such as stratum corneum surface roughness, but also any internal change in the skin that does not systematically manifest as altered appearance, such as dermal thinning. "photoaging" refers to the premature aging of skin caused by prolonged and cumulative exposure to the sun.

Preferably, the present invention relates to the use of a composition as described above for improving the barrier function of the skin and the hydration of the epidermis.

Finally, a final object of the invention relates to a cosmetic treatment method characterized in that a composition comprising an effective amount of a peptide compound according to the invention is topically applied to the skin or keratinous appendages to be treated, in order to prevent and/or treat the signs of skin ageing and photoaging and to prevent and/or repair damages caused by UV radiation. In a specific embodiment, the composition is applied before the skin is exposed to the sun and is therefore an excellent pre-treatment to prevent damage at the DNA level.

In a second embodiment of the invention, the composition is applied to the skin as a post-sun treatment to repair any skin damage at the DNA level.

In a last preferred embodiment of the invention, the composition is applied in the morning as an anti-aging daytime care or before bedtime as a nighttime restorative care. If used as a daytime care, the composition will provide skin protection against environmental insults such as UVB radiation by limiting the occurrence of DNA level damage. As a nighttime care, the composition will work by repairing daytime induced skin damage.

Drawings

FIG. 1 is a histogram showing the results of immunoblotting with Normal Human Keratinocytes (NHK) transfected with siRNA/caspase-14 gene.

Fig. 2a and 2b are histograms showing the results of 2 comet (comet) tests performed on Normal Human Keratinocytes (NHK) subjected to UV radiation.

The following examples describe and demonstrate the efficacy of peptide compounds, such as those described herein, but should not be construed as limiting the invention.

Examples

Example 1: studies of caspase-14 expression in normal human keratinocytes in the presence of the peptide SEQ ID No. 2

The aim of this study was to determine the expression of caspase-14 in normal human keratinocytes treated or not by the peptides of the invention:

scheme(s)

Cultured normal human keratinocytes NHK were treated with 1% or 3% peptide SEQ ID No. 2 for 24 hours. The cells were then washed, fixed with 3.7% -paraformaldehyde, and washed with BSA (diluted to 1/100)^th) In the presence of 0.1% -triton. Cells were incubated in the presence of caspase-14-specific mouse monoclonal antibody (BDbiosciences) and then in the presence of secondary antibody coupled to a fluorescent label. The cells were then examined by epifluorescence microscopy (nikoneclipse 600 microscope).

Results

An increase in light intensity was observed in peptide-treated NHK cells relative to control conditions. This increase in fluorescence was dose dependent, as fluorescence was stronger when 3% peptide solution was added than when 1%. Thus, the peptide of SEQ ID No. 2 activates caspase-14 expression in NHK.

Example 2: study of caspase-14 expression by siRNA in HNK treated with peptide SEQ ID No. 2

To quantify the efficacy of the peptides of the invention on caspase-14 overexpression in the NHK population, the gene encoding caspase-14 was "eliminated" using siRNA technology.

Scheme(s)

NHK cells were cultured to 60% confluence in 6-well plates and then treated with 20. mu.L of 1% -peptide SEQ ID No. 2. Then, 100. mu.L of the previously prepared mixture of caspase-14 containing siRNA and transfection reagent was carefully added dropwise well by well. Will be thinCell culture plates at 37 ℃ and 5% CO₂The mixture was incubated for 72 hours. The medium was changed every 2 days. 4 conditions were carried out:

-condition 1: control without siRNA and peptide active ingredient

-condition 2: siRNA-transfected cells, free of peptide active ingredients

-condition 3: untransfected cells but treated with peptide active ingredients

-condition 4: cells transfected with siRNA and treated with peptide active ingredients

Quantification of caspase-14 expression was observed using conventional immunoblotting techniques (western blot) by anti-caspase-14 antibodies and according to conventional protocols. To analyze the compensation brought by the peptide in NHK transfected with siRNA, comparison was made with untreated NHK whose gene was not eliminated by siRNA.

Results

Between conditions 1 and 3, it was found that the addition of the peptide resulted in a 20.9% increase in caspase-14 protein expression relative to the control. Between conditions 1 and 2, the effect of siRNA on caspase-14 protein expression is clearly seen: the lower by 30.6%. However, addition of the peptide of SEQ ID No. 2 to cells transfected with siRNA helped to restore caspase-14, and then only 14% reduction due to the presence of siRNA relative to control conditions.

The conclusion is that the peptide of the invention of SEQ ID No. 2 increases caspase-14 expression in NHK.

Example 3: studies of profilaggrin/filaggrin expression in human skin biopsies in the presence of the peptide SEQ ID No. 1

The objective of this study was to determine the effect of the peptides of the invention on the amount of filaggrin and filaggrin (hereafter referred to as filaggrin/filaggrin) in a human skin biopsy.

Scheme(s)

Samples of human skin were incubated at the air/liquid interface. Under the first condition, the samples were treated with 1% peptide SEQ ID No:1 for 24 hours and 72 hours. Under the second condition, the samples were treated with the same peptide but at a concentration of 3% for 24 hours and 72 hours.

These skin samples were then fixed with formaldehyde and then embedded in paraffin. Then, slices of 2 to 3 μm in size were prepared. Immunostaining was performed after exposure of specific sites by incubation in pepsin. Immunostaining was then performed by a filaggrin-specific mouse monoclonal antibody (tebu santa cruz), followed by a secondary antibody conjugated with a fluorescent label. The skin sections were then examined using an epifluorescence microscope (nikoneclipse 600 microscope).

Results

An increase in pro/filaggrin staining was observed on biopsies treated with the peptides of the invention. Note that staining was not only dose dependent, but it increased over time (between 24 and 72 hour conditions). It can thus be concluded that the peptide of SEQ ID No. 1 allows an increase in the cleavage of profilaggrin into filaggrin by an increase in caspase-14 expression and/or activity.

Example 4: comet assay for NHK cells

The comet test is a test that allows quantification of DNA damage at the cellular level.

Scheme(s)

For this purpose, NHK cells:

-under condition a: incubated with 1% and 3% peptide compounds of the sequence SEQ ID No. 3 for 24 hours and then at 20mJ/cm²To observe the protective effect of the peptide active ingredient on the cells;

-under condition b: in the first step, 20mJ/cm is used²UVB radiation ofThe peptide compounds were then treated for 24 hours with concentrations of 1% and 3% to observe the repairing effect of the active ingredient on the cells.

In each case, the control conditions were achieved by the absence of peptide active ingredient.

The cells were then removed from their carrier by trypsinization (trypsinization), then centrifuged at 900rpm for 5 minutes before concentration and counting.

The specific cell count (25,000 cells) was then incorporated into a 0.75% low melting agarose gel and then deposited on a slide previously coated with 1% agarose. The slides were then immersed in lysis buffer for 1.5 hours at 4 ℃ and then in alkaline solution for 20 minutes at 4 ℃. The cells are then lysed and the DNA is denatured. The slide was immersed in the electrophoretic solution, and then an electric field (20V-250 mA) was applied. Thus, the denatured DNA was allowed to migrate in an agarose gel at 4 ℃. DNA fluorescent dye (2 μ g/ml propidium iodide) was applied on the slide so that DNA in the case of damage was observed in comet form.

Quantitative software was used to determine the average tail moment (TailMoment) applied to each test condition. This parameter provides information on the level of DNA damage: the higher this parameter, the greater the DNA damage.

Results

The results are shown in FIGS. 2a and 2 b. Under condition a, when the peptide was applied as a pretreatment (at a concentration of 1% or 3%), the tail moment was reduced by 57%, i.e. the cells suffered less damage than under the control conditions where UVB radiation was applied. These results clearly demonstrate the protective effect of the peptide compound of SEQ ID No. 3 on NHK cells. Furthermore, when the peptide was administered after irradiation without any pretreatment (condition b), the tail moment was reduced by 31% when the peptide was administered at a concentration of 1%. When the peptide was administered at a concentration of 3%, the tail moment was reduced by 58%. This test under condition b confirms the remedial effect of the peptide SEQ ID No. 3 on DNA under UV irradiation.

Example 5: confirmation of the efficacy of the peptide SEQ ID No. 2 on human skin biopsies subjected to UVB radiation

The purpose of this experiment was to measure the ability of the peptide compounds of the invention to repair after exposure of human skin biopsies to UVB radiation. UV radiation, in particular UVB radiation, induces a dimerization reaction that takes place at a site comprising two adjacent pyrimidines (thymidine, cytosine). Several types of photoproducts were then formed, among which cyclobutane-pyrimidine dimers or CPD. However, it is known that when cells are subjected to genotoxic stress, their division cycle is temporarily halted to allow DNA repair and to avoid mutations within subsequent cell generations. Cell proliferation continued only thereafter. If the rate or amount of damage is too high, or if repair is ineffective, the cell triggers the programmed cell death process to apoptosis. Thus, measuring the amount of photoproduct formed by immunostaining with anti-CPD antibodies allows to evaluate the effectiveness of compounds with DNA repair action.

CPD immunostaining protocol on skin biopsies receiving UVB radiation

Human skin biopsies were cultured at the air/liquid interface. These biopsies were taken at 200mJ/cm²UVB radiation. After irradiation, a 1% -solution of the peptide SIQIDNo:2 was applied topically to the biopsy for 24 hours under the first conditions. Under the second condition, a 3% -solution of peptide SIQIDNo:2 was topically applied for 24 hours. Control conditions were achieved by topical application of PBS solution after irradiation.

To stain cyclobutane-pyrimidine dimers, skin biopsies were wrapped in paraffin and 3 μm thick tissue sections were prepared. Slides were dewaxed, hydrated, and immunostained with an antibody against cyclobutane-pyrimidine dimer (MBLD194-1, mouse monoclonal) followed by a suitable secondary antibody (invitrogen a21202) conjugated with a fluorescent label. The skin sections were then examined with an epifluorescence microscope (nikoneclipse 80i microscope).

Results

Under control conditions, strong fluorescence was observed when biopsies were subjected to UVB radiation. Under both conditions tested with the peptide SEQ ID No. 2 post-treatment, much weaker fluorescence was observed than the control conditions with UVB radiation.

Conclusion

The peptide seq id No. 2 provides better and more significant DNA damage repair, particularly as a result of caspase-14 activation. It was also observed that this repair effect was dose-dependent, since the repair effect was more pronounced with higher amounts of active ingredient administered.

Example 6: sunscreen composition

Claims (19)

1. A peptide compound of the following general formula (I):

R₁–(AA)_n–X₁–X₂–Ile–Gln–Ala–Cys–Arg–Gly–X₃–(AA)_p–R₂wherein

X₁Aspartic acid, glutamic acid or no amino acid;

X₂asparagine, proline, serine or no amino acid;

X₃asparagine, arginine, leucine or no amino acid;

AA is any amino acid, and n and p are integers from 0 to 2;

R₁a primary amine function which is a free N-terminal amino acid;

R₂a hydroxyl group which is a carboxyl function of the C-terminal amino acid, which may be selected from C₁-C₃₀Alkyl chain substituted by a group, or NH2, NHY or NYY, wherein Y is C₁-C₄An alkyl chain;

the sequence of formula (I) comprises 6-13 amino acid residues,

said peptide compound of general formula (I) being characterized in that it corresponds to one of the following formulae:

(SEQIDNo:1)Asp–Pro–Ile–Gln–Ala–Cys–Arg–Gly–NH₂

(SEQIDNo:2)Ile–Gln–Ala–Cys–Arg–Gly–NH₂

(SEQIDNo:3)Asn–Arg–Ile–Gln–Ala–Cys–Arg–Gly–NH₂。

2. peptide compound according to claim 1, characterized in that it is dissolved in one or more physiologically suitable solvents selected from the group consisting of: water, glycerol, ethanol, propylene glycol, butylene glycol, dipropylene glycol, ethoxylated or propoxylated diethylene glycol, cyclic polyols or any mixture of these solvents.

3. Peptide compound according to claim 1 or 2, characterized in that it is used as a medicament.

4. A cosmetic composition comprising the peptide compound of claim 1 or 2 as an active ingredient.

5. Cosmetic composition according to claim 4, characterized in that it is in a form suitable for topical application, comprising a cosmetically acceptable medium.

6. The composition according to claim 4 or 5, characterized in that the peptide compound is present in the composition at a concentration of 0.0005-500 ppm.

7. The composition of claim 6, wherein said peptide compound is present in said composition at a concentration of 0.01 to 5 ppm.

8. The composition according to claim 4 or 5, characterized in that it further comprises at least one other active ingredient which promotes the action of the peptide compound.

9. A composition according to claim 8, characterized in that the active ingredient is a substance with anti-wrinkle activity, said substance being a free radical scavenger or an antioxidant, or a substance stimulating the synthesis of dermal macromolecules, or a substance stimulating energy metabolism.

10. Use of a peptidic compound as defined in claim 1 or 2 for the preparation of a cosmetic composition for preventing and/or repairing DNA damage and activating caspase-14 and filaggrin formation.

11. Use according to claim 10, characterized in that the damage is induced by UV radiation.

12. Use according to claim 10, for preventing and/or treating the signs of skin aging and photoaging.

13. Use according to claim 12, characterized in that the signs of skin ageing are wrinkles, cracks, sagging of the skin and the subcutaneous tissue, loss of skin elasticity and stiffness, loss of firmness and tone and atrophy of the dermis.

14. The use according to claim 13, wherein said wrinkles comprise deep coarse wrinkles and fine wrinkles.

15. Use according to claim 10 for improving skin barrier function and epidermal hydration.

16. Use of a peptidic compound as defined in claim 1 or 2 for the preparation of a composition for topical application to the skin for preventing and/or treating the signs of skin aging and photoaging, and preventing and/or repairing damage caused by UV radiation.

17. Use according to claim 16, characterized in that the composition is applied as a pre-sun care to prevent damage at the DNA level prior to exposure to the sun.

18. Use according to claim 16, characterized in that the composition is applied as a post-sun care after exposure to the sun to repair damage at the DNA level.

19. Use according to claim 16, characterized in that the composition is applied in the morning as an anti-aging daytime care or before bedtime as a nighttime restorative care.