WO2013088369A2 - Use of the protein mmp-12 in the prevention and/or treatment of greasy skin and/or greasy-prone skin - Google Patents

Abstract

The present invention relates to the cosmetic use of an effective amount of at least one active agent consisting of a polypeptide having at least 80% amino acid identity with a metalloprotease MMP-12 whose sequence is chosen from SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3 indicated below, or a C-terminal fragment of this polypeptide, for preventing and/or treating greasy skin and/or greasy-prone skin, the said polypeptide or the said fragment comprising the sequence KDXK, in which X represents aspartic acid or glutamic acid.

Description

USE OF THE PROTEIN MMP-12 IN THE PREVENTION AND/OR TREATMENT OF GREASY SKIN AND/OR GREASY-PRONE SKIN The present invention is directed mainly towards proposing a novel active agent for preventing and/or treating greasy skin and/or greasy-prone skin.

The present invention relates to the use, especially the cosmetic use, of an effective amount of at least one novel active agent for preventing and/or treating greasy skin and/or greasy-prone skin, especially via an action on reducing the secretion of sebum.

Sebum is normally an agent for moisturizing the epidermis.

It is the natural product of the sebaceous gland, which is an annex of the pilosebaceous unit. It is essentially a more or less complex mixture of lipids. Conventionally, the sebaceous gland produces squalene, triglycerides, aliphatic waxes, cholesterol waxes and, possibly, free cholesterol (Stewart, M.E., Semin. Dermatol. 11, 100-105 (1992)). The action of bacterial lipases converts a variable proportion of the triglycerides formed into free fatty acids.

The sebocyte constitutes the competent cell of the sebaceous gland. The production of sebum is associated with a programme of terminal differentiation of this cell. During this differentiation, the metabolic activity of the sebocyte is essentially directed towards the biosynthesis of lipids (lipogenesis) and more precisely to fatty acid neosynthesis.

Hyperseborrhoeic fatty skin is characterized by an exaggerated secretion and excretion of sebum. Conventionally, a sebum level of greater than 200 μg/cm² measured on the forehead is considered as being characteristic of such greasy skin. Such skin is also often associated with a desquamation defect, a shiny complexion or a thick skin grain, which manifestations are perceived as being skin imperfections or aesthetic disorders.

Besides its unsightly appearance, it constitutes terrain on which complications may arise. It affects the areas in which the sebaceous glands are numerous and results mainly from androgenic overstimulation of sebum production by these specific glands. Thus, hyperseborrhoea participates in the appearance of common acne lesions.

Common acne is a multi-factor pathology that attacks skin rich in sebaceous glands (face, shoulder area, arms and intertriginous areas). It is one of the most common forms of dermatosis.

In its mildest form, this dermatosis affects almost all humans. Its frequency is maximal at the age of puberty, but it may appear for the first time from the age of 7 to 9 and may extend beyond the age of 40. It also equally affects men and women. Among its commonest forms, mention may be made of comedonal acne, commonly referred to as juvenile acne, papulo -pustular and/or nodular acne, acne conglobata and "exogenous" acne appearing in reaction to inflammatory external factors.

More specifically, acne is a pathology of the sebaceous gland follicle. The following five pathogenic factors play a determining role in the formation of acne:

- genetic predisposition,

- overproduction of sebum (seborrhoea),

- androgen,

- follicular keratinization disorders (comedogenesis), and

- bacterial colonization and inflammatory factors.

Specifically, in the deepest parts of the infundibular portion of the hair follicle, the formation of a larger than normal amount of keratinocytes is observed. These cells differentiate into horny cells which gradually obstruct the lumen of the follicular duct. The physiological process of continuous desquamation from the acro-infundibulum to the surface is disrupted by the increased adherence of the horny cells produced. A hyperkeratosic plug forms, which constitutes the comedone, the initial acne lesion. Finally, the three predominant local microorganisms Staphylococcus epidermidis, Malassezia furfur and Propionibacterium acnes find in the sebaceous follicle an ideal nutritive medium.

Impairment of the medium and the improvement of the growth conditions for the microflora lead to an increase in pro-inflammatory products such as lipases, proteases and interleukins. It is accepted that the lipases produced dissociate the triglycerides into free fatty acids, which act as irritants on the follicular epithelium and subsequently stimulate hyperproliferation. Due to the intensification of the inflammatory process, granulocytes are attracted and migrate into the lumen of the follicle, where they finally contribute towards the enzymatic rupture of the follicular wall.

The clinical "retention" manifestations observed may be of open or closed comedone type (microcysts, microcomedones or whiteheads). The inflammatory lesions derived from the retention lesions may be of the type such as papules, pustules, with indurated nodules, abscesses, fistules or scar forms.

Thus, acneic and acne-prone individuals usually have greasy, greasy-prone or combination skin. Their skin is usually shiny with numerous imperfections on the face, inter alia (microcysts, microcomedones, whiteheads, papules, pustules, with indurated nodules, abscesses, fistules or scar forms). The imperfections may also be of the type such as dull, off- colour skin, dyschromia, redness, or rough skin with dry skin plaques. Cutaneous hyperkeratosis is observed, the facial pores are dilated, the skin is often rough with a thick stratum corneum revealing in plaques areas of dry skin (epidermal atrophy and mild desquamation).

Consequently, hyperseborrhoeia is manifestly a biological phenomenon that it is important to control effectively in order to prevent the manifestation of the associated skin disorders.

To combat hyperseborrhoea, the prior art has already proposed various compounds, which, by topical application to the skin, are capable of reducing the lipogenesis of the sebocytes and consequently of limiting the production of sebum.

Unfortunately, the treatments currently available are not entirely satisfactory, especially with regard to the side effects that are frequently associated therewith, such as irritant effects with certain topical agents such as retinoids and benzoyl peroxides, or even gastrointestinal effects (oral antibiotic therapy). In addition, resistance of P. acnes to certain local antibacterial therapies is frequently observed.

There is thus still a need for novel active agents that are capable of exerting beneficial cosmetic or therapeutic action on greasy skin or greasy-prone skin.

There is also still a need for active agents that can re-establish the eco flora of greasy skin.

There is also a need for novel compositions that are effective in preventing and/or treating greasy skin or greasy-prone skin and that are pleasant and comfortable to use, thus promoting adherence to the treatment.

There is also a need for novel active agents for preventing and/or treating greasy skin disorders, especially such as seborrhoeic dermatitis and in particular acne.

The object of the present invention is to satisfy these needs.

Thus, according to a first subject, the invention relates to the cosmetic use of an effective amount of at least one active agent consisting of a polypeptide having at least 80% amino acid identity with a metalloprotease MMP-12 whose sequence is chosen from SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3 indicated below, or a C-terminal fragment of this polypeptide, for preventing and/or treating greasy skin and/or greasy-prone skin, the said polypeptide or the said fragment comprising the sequence KDXK, in which X represents aspartic acid or glutamic acid. This decrease obtained with the aid of the active agent according to the invention thus contributes towards re-establishing an equilibrated ecoflora on the skin, the consequence of which is a reduction in the inflammatory condition of the skin and regulation of the seborrhoea. Consequently, the imperfections diminish, the skin lightens and becomes more uniform, with no areas of dyschromia or any dryness.

According to another of its aspects, the present invention relates to a polypeptide with at least 80% amino acid identity with the metalloprotease MMP-12 whose sequence is chosen from SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, or a C-terminal fragment of the said polypeptide, for its use as an active agent in a pharmaceutical or dermatological composition for preventing and/or treating skin infections caused by Malassezia furfur, Propionibacterium acnes and/or Propionibacterium granulosum, the said polypeptide or the said fragment comprising the sequence KDXK, in which X represents aspartic acid or glutamic acid.

In certain embodiments, the prevention and treatment of the various skin conditions defined in the present description excludes the prevention and/or treatment of scalp conditions, and especially excludes the prevention and/or treatment of dandruff conditions of the scalp and the prevention and/or treatment of bacterial or fungal infections of the scalp, including scalp infections with Malassezia sp.

According to another of its aspects, the present invention relates to a cosmetic and/or dermatological composition for preventing and/or treating greasy skin or greasy-prone skin and the associated aesthetic disorders, comprising, in a physiologically acceptable medium, at least one active agent in accordance with the invention, in combination with an effective amount of at least one additional agent for reducing and/or correcting the excessive secretion of sebum, for example an anti-seborrhoeic agent, especially such as described below, this additional agent being different from the active agent according to the invention.

According to the present invention, such a composition is intended to be used orally and/or parenterally, especially topically.

According to another of its aspects, the present invention relates to a process, especially a cosmetic process, for treating and/or preventing greasy skin or greasy-prone skin and the associated skin disorders, especially aesthetic disorders, in an individual, comprising at least one step of administering to the said individual at least an effective amount of at least one active agent according to the invention, consisting of a polypeptide having at least 80% amino acid identity with the metalloprotease MMP-12 whose sequence is chosen from SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, or a C-terminal fragment of the said polypeptide, the said polypeptide or the said fragment comprising the sequence KDXK, in which X represents aspartic acid or glutamic acid.

According to one embodiment variant of the invention, an active agent in accordance with the invention is used orally.

According to another embodiment variant of the invention, an active agent in accordance with the invention is used parenterally, preferably topically.

As stated below, the compositions containing it are formulated to be compatible with the adopted mode of administration.

The term "physiologically acceptable medium" means a medium that is compatible with all keratin materials such as the skin, the scalp, the nails, mucous membranes, the eyes and the hair, or any other area of bodily skin, and especially with the skin. A physiologically acceptable medium is preferentially a cosmetically or dermato logically acceptable medium, i.e. a medium that has no unpleasant odour, colour or appearance, and that is entirely compatible with the route of administration under consideration, namely the oral and/or parenteral route, especially the topical route.

According to the invention, the terms "preventing" and "prevention" mean reducing the risk of occurrence or slowing down the occurrence of a given phenomenon, for instance, according to one aspect of the present invention, excessive colonization of the skin, especially greasy skin or greasy-prone skin, by Malassezia furfur, Propionibacterium acnes and/or Propionibacterium granulosum.

For the purposes of the invention, the term "effective amount" means the minimum amount that is sufficient to observe the occurrence of the desired effect, namely, for example, the treatment of skin disorders associated with greasy skin and/or greasy-prone skin. Such an amount may be determined by any method known to those skilled in the art, for example by means of preliminary experimental tests.

Active agent derived from the metalloprotease VI VI P- 12

The present invention relates to the use of an effective amount of an active agent consisting of a polypeptide having at least 80% amino acid identity with the metalloprotease MMP-12 of SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3 indicated below, or a C- terminal fragment of this polypeptide, as an active agent, the said polypeptide or the said fragment comprising the sequence KDXK, in which X represents aspartic acid or glutamic acid.

The matrix metalloprotease MMP-12, or MMP-12, is a metalloprotease belonging to the family of matrix metalloproteases, which are enzymes that especially have the role of degrading the extracellular matrix of connective tissues, and especially of the skin. This family of enzymes plays an important role in a large number of essential physiological processes, such as morphogenesis, angiogenesis and tissue repair.

MMP-12, also known under the name macrophage lipase, is especially known for its role in degrading elastin.

However, when they are expressed aberrantly or excessively, these enzymes may lead to the appearance of pathologies.

Thus, the role of MMP-12 in a certain number of pathologies such as arthritis, emphysema (Hautamaki et al. Macrophage elastase is required for cigarette smoke-induced emphysema in mice. Science 277, 2002-2004 (1997)) and vascular diseases (Curci et al. Expression and localization of macrophage elastase (matrix metalloproteinase-12) in abdominal aortic aneurysms. J. Clin. Invest. 102, 1900-1910 (1998)) has been demonstrated.

However, to the Applicant's knowledge, an activity of MMP-12 in relation with skin disorders associated with greasy skin or greasy-prone skin has never been described in the prior art.

For the purposes of the present invention, the "percentage of identity" between two amino acid sequences is determined by comparing the two optimally aligned sequences, by means of a comparison window.

The part of the amino acid sequence in the comparison window may thus comprise additions or deletions (for example "gaps") relative to the reference sequence (which does not comprise these additions or these deletions) so as to obtain an optimal alignment between the two sequences.

The percentage of identity is calculated by determining the number of positions at which an identical amino acid is observed for the two compared sequences, followed by dividing the number of positions at which there is identity between the two amino acids by the total number of positions in the comparison window, and then multiplying the result by 100 in order to obtain the percentage of amino acid identity between the two sequences.

The optimal alignment of the sequences for the comparison may be achieved by computer using known algorithms. In an entirely preferred manner, the percentage of sequence identity is determined using the CLUSTAL W software (version 1.82), the parameters being set as follows: (1) CPU MODE = ClustalW mp (2) ALIGNMENT = " full "; (3) OUTPUT FORMAT = " aln w/numbers " (4) OUTPUT ORDER = " aligned "; (5) COLOR ALIGNMENT = " no " (6) KTUP (word size) = " default "; (7) WINDOW LENGTH = " default "; (8) SCORE TYPE = " percent "; (9) TOPDIAG = " default "; (10) PAIRGAP = " default "; (11) PHYLOGENETIC TREE/TREE TYPE = " none "; (12) MATRIX = " default "; (13) GAP OPEN = " default "; (14) END GAPS = " default "; (15) GAP EXTENSION = " default "; (16) GAP DISTANCES = " default "; (17) TREE TYPE = " cladogram " and (18) TREE GAP DISTANCES = " hide ".

A polypeptide or a C-terminal fragment thereof according to the invention may be synthesized via standard methods of synthetic chemistry, i.e. homogeneous chemical syntheses in solution or in solid phase. By way of illustration, a person skilled in the art may use the solution polypeptide synthetic techniques described by Houben-Weyl (1974, in Methode der Organischen Chemie, E. Wunsh ed., volume 15-1 and 15 -II, Thieme, Stuttgart.). A polypeptide or a C-terminal fragment thereof according to the invention may also be synthesized chemically in liquid or solid phase by successive coupling of the various amino acid residues (from the N-terminal end to the C-terminal end in the liquid phase, or from the C-terminal end to the N-terminal end in the solid phase). A person skilled in the art may especially use the solid-phase peptide synthesis technique described by Merrifield (Merrifield R.B., (1965a), Nature, vol. 207 (996): 522-523; Merrifield R.B., (1965b), Science, vol. 150 (693): 178-185.)

According to another aspect, a polypeptide or a C-terminal fragment thereof according to the invention may be synthesized by genetic recombination, for example according to a production process comprising the following steps:

(a) preparing an expression vector into which has been inserted a nucleic acid coding for the polypeptide or a C-terminal fragment thereof of the invention, the said vector also comprising the regulatory sequences necessary for the expression of the said nucleic acid in a chosen host cell;

(b) transfecting a host cell with the recombinant vector obtained in step (a);

(c) culturing the host cell transfected in step b) in a suitable culture medium; (d) recovering the culture supernatant of the transfected cells or the cell lysate of the said cells, for example by sonication or by osmotic shock; and

(e) separating or purifying, from the said culture medium, or from the cell lysate pellet, the recombinant polypeptide or a recombinant C-terminal fragment thereof of the invention.

To purify a polypeptide or a C-terminal fragment thereof according to the invention that has been produced by host cells transfected or infected with a recombinant vector coding for the said polypeptide or a C-terminal fragment thereof, a person skilled in the art may advantageously use purification techniques described by Molinier-Frenkel (2002, J. Viral. 76, 127-135), by Karayan et al. (1994, Virology 782-795) or by Novelli et al. (1991, Virology 185, 365-376).

Preferably, the MMP-12 under consideration according to the invention is human and of sequence SEQ ID NO: 1 as defined in the present patent application.

According to one embodiment of the invention, a fragment of the C-terminal part of a polypeptide in accordance with the invention may also be used, on condition, however, that this fragment comprises the amino acid sequence KDXK.

K represents a lysine (abbreviated as Leu) and D represents an aspartic acid (abbreviated as Asp).

The amino acid defined as being X in the amino acid sequence KDXK mentioned previously is chosen from glutamic acid (abbreviated as Glu or E) and aspartic acid

(abbreviated as Asp or D).

Such a C-terminal fragment that is suitable for use in the invention may comprise a sequence with a length of 80 to 20 contiguous amino acids, or even 50 to 20 contiguous amino acids, and preferably 30 to 20 contiguous amino acids at the C-terminal end of the polypeptide.

According to one preferred embodiment, a C-terminal fragment of a polypeptide in accordance with the invention consists at least, contiguously and in this order, of at least the 8 amino acids preceding the sequence KDXK according to the invention, the sequence KDXK itself, and then at least the 8 amino acids following the sequence KDXK in a polypeptide in accordance with the invention.

According to one preferred embodiment of the invention, the C-terminal fragment of a polypeptide in accordance with the invention, i.e. having at least 80% amino acid identity with the metalloprotease MMP-12 whose sequence is chosen from SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3 is chosen from the following sequences:

SEQ ID NO: 4: ARNQ VFLFKDDKY WLI SNLR

SEQ ID NO: 5: GRNQLFLFKDEKYWLINNLV

SEQ ID NO: 6: SRNQLFLFKDEKYWLINNLV

According to one preferred embodiment, at least the amino acids constituting the sequence KDXK are in beta form.

According to one embodiment of the invention, an active agent in accordance with the invention consisting of a polypeptide having at least 80% amino acid identity with the metalloprotease MMP-12 of sequence SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3 indicated below, or a C-terminal fragment of this polypeptide, the said polypeptide or the said fragment comprising the sequence KDXK, in which X represents aspartic acid or glutamic acid, is used in a composition, especially a cosmetic composition, as defined below.

The active agent according to the invention may be present in a composition in a content of between 0.0001% and 30%> by weight, preferably between 0.001% and 15% by weight and preferentially between 0.1% and 10% by weight relative to the total weight of the composition.

According to one embodiment variant, an active agent in accordance with the invention may be included in a composition of the invention in the form of a lyophilized powder, where appropriate in a concentrated form.

Composition

The present invention relates to a cosmetic and/or dermatological composition that is useful for preventing and/or treating greasy skin or greasy-prone skin and the associated aesthetic disorders, comprising, in a physiologically acceptable medium, at least one active agent as defined previously.

The aesthetic disorders in accordance with the invention may be chosen especially from a desquamation defect, a shiny complexion and a thick skin grain.

Such a composition also comprises at least an effective amount of at least one additional agent for reducing or correcting excessive secretion of sebum, for example an anti- seborrhoeic agent especially as described below, this additional agent being different from the active agent according to the invention.

The term "anti-seborrhoeic agent" means a compound that is capable of regulating the activity of the sebaceous glands.

An anti-seborrhoeic agent that is suitable for use in the invention may be chosen especially from retinoic acid, benzoyl peroxide, sulfur, vitamin B6 (or pyridoxine), selenium chloride and sea fennel; mixtures of extract of cinnamon, of tea and of octanoylglycine such as Sepicontrol A5 TEA® from SEPPIC; the mixture of cinnamon, sarcosine and octanoylglycine sold especially by the company SEPPIC under the trade name Sepicontrol A5®; zinc salts such as zinc gluconate, zinc pyrrolidonecarboxylate (or zinc pidolate), zinc lactate, zinc aspartate, zinc carboxylate, zinc salicylate and zinc cysteate; copper derivatives and in particular copper pidolate such as Cuivridone® from Solabia; extracts of plants of the species Arnica montana, Cinchona succirubra, Eugenia caryophyllata, Humulus lupulus, Hypericum perforatum, Mentha piperita, Rosmarinus officinalis, Salvia officinalis and Thymus vulgaris, all sold, for example, by the company Maruzen; extracts of meadowsweet {Spiraea ulmaria), such as the product sold under the name Sebonormine® by the company Silab; extracts of the alga Laminaria saccharina, such as the product sold under the name Phlorogine® by the company Biotechmarine; mixtures of extracts of salad burnet root (Sanguisorba officinalis/Poterium officinale), of ginger rhizomes (Zingiber officinalis) and of cinnamon bark (Cinnamomum cassia), such as the product sold under the name Sebustop® by the company Solabia; linseed extracts, such as the product sold under the name Linumine® by the company Lucas Meyer; Phellodendron extracts, such as those sold under the name Phellodendron extract BG by the company Maruzen or Oubaku liquid B by the company Ichimaru Pharcos; mixtures of argan oil, of Serenoa serrulata (saw palmetto) extract and of sesame seed extract, such as the product sold under the name Regu SEB® by the company Pentapharm; mixtures of extracts of willowherb, of Terminalia chebula, of nasturtium and of bioavailable zinc (microalgae), such as the product sold under the name Seborilys® by the company Green Tech; extracts of Pygeum africanum, such as the product sold under the name Pygeum africanum sterolic lipid extract by the company Euromed; extracts of Serenoa serrulata, such as the products sold under the name Viapure Sabal by the company Actives International or those sold by the company Euromed; mixtures of extracts of plantain (Plantago sp , of Berberis aquifolium and of sodium salicylate, such as the product sold under the name Seboclear® by the company Rahn; clove extract, such as the product sold under the name Clove extract powder by the company Maruzen; argan oil, such as the product sold under the name Lipofructyl® by Laboratoires Serobiologiques; lactic protein filtrates, such as the product sold under the name Normaseb® by the company Sederma; extracts of the alga Laminaria, such as the product sold under the name Laminarghane® by the company Biotechmarine; oligosaccharides of the alga Laminaria digitata, such as the product sold under the name Phycosaccharide AC by the company Codif; sugar cane extracts, such as the product sold under the name Policosonol® by the company Sabinsa; sulfonated shale oil, such as the product sold under the name Ichthyol Pale® by the company Ichthyol; European meadowsweet (Spiraea ulmaria) extracts, such as the product sold under the name Cytobiol® Ulmaire by the company Libiol; sebacic acid, especially sold in the form of a sodium polyacrylate gel under the name Sebosoft® by the company Sederma; glucomannans extracted from konjac tuber and modified with alkylsulfonate chains, such as the product sold under the name Biopol Beta by the company Arch Chemical; extracts of Sophora angustifolia, such as those sold under the name Sophora powder or Sophora extract by the company Bio land; extracts of Cinchona succirubra bark, such as the product sold under the name Red Bark HS by the company Alban Muller; extracts of Quillaja saponaria, such as the product sold under the name Panama wood HS by the company Alban Muller; glycine grafted onto an undecylenic chain, such as the product sold under the name Lipacide UG OR by the company SEPPIC; the mixture of oleanolic acid and of nordihydroguaiaretic acid, such as the product sold in the form of a gel under the name AC.Net by the company Sederma; phthalimidoperoxyhexanoic acid; tri(Ci₂-Ci₃)alkyl citrate sold under the name Cosmacol® ECI by the company Sasol; tri(Ci₄-Ci₅)alkyl citrate sold under the name Cosmacol® ECL by the company Sasol; 10-hydroxydecanoic acid, and especially mixtures of 10-hydroxydecanoic acid, of sebacic acid and of 1,10-decanediol, such as the product sold under the name Acnacidol® BG by the company Vincience; and mixtures thereof.

Preferably, an anti-seborrhoeic agent according to the invention may be chosen from sugar cane extracts such as the product sold under the name Policosanol^® by the company Sabinsa, extracts of the alga Laminaria, such as the product sold under the name Laminarghane^® by the company Biotechmarine, extract of burdock, extract of wild pansy and essential oils of thyme.

Such additional anti-seborrhoeic agents may be present in a composition in accordance with the invention in a content of between 0.01% and 20% by weight, preferably between 0.1% and 10% by weight and preferentially between 0.1% and 5% by weight relative to the total weight of the composition.

Besides this anti-seborrhoeic agent, may also contain several other commonly used and/or permitted agents, these other agents being different from the active agent according to the invention.

As active agents that are conventionally used, mention may be made of vitamins B3, B5, B6, B8, C, D, E and PP, niacin, carotenoids, polyphenols, minerals and trace elements, phytoestrogens, proteins and amino acids, mono- and polysaccharides, amino sugars, phytosterols and triterpene alcohols of plant origin.

The minerals and trace elements particularly used are zinc, calcium, magnesium, copper, iron, iodine, manganese, selenium and chromium (III).

Among the polyphenols, polyphenols from grape, from tea, from olive, from cocoa, from coffee, from apple, from blueberry, from elderberry, from strawberry, from cranberry and from onion are also selected in particular. Preferably, among the phytoestrogens, isoflavones in free or glycosylated form, such as genistein, daidzein or glycitein, or lignans, in particular those from flax and from Schizandra chinensis, are selected.

A composition according to the invention may also comprise at least one antioxidant, other than the active agent according to the invention.

An additional antioxidant in accordance with the invention may be chosen from tocopherol and esters thereof, in particular tocopheryl acetate; ascorbic acid and derivatives thereof, in particular magnesium ascorbyl phosphate and ascorbyl glucoside; ferulic acid; serine; ellagic acid, phloretin, polyphenols, tannins, tannic acid, epigallocatechins and natural extracts containing them, anthocyans, rosemary extracts, olive leaf extracts, for instance those from the company Silab, green tea extracts, resveratrol and derivatives thereof, ergothioneine, N-acetylcysteine, an extract of the brown alga Pelvetia caniculata, for instance Pelvetiane® from Secma, chlorogenic acid, biotin, chelating agents, such as BHT and BHA, Ν,Ν'- bis(3,4,5-trimethoxybenzyl)ethylenediamine and salts thereof; idebenone, plant extracts, for instance Pronalen Bioprotect TM from the company Provital; coenzyme Q10, bioflavonoids, SODs, phytanetriol, lignans, melatonin, pidolates, glutathione, caprylyl glycol, phloretin, Totarol™ or extract of Podocarpus totara containing Totarol (totara-8,11,13-trienol or 2- phenanthrenol, 4b,5,6,7,8,8a,9,10-octahydro-4b,8,8-trimethyl-l-(l-methylethyl)-; a jasmine extract such as the product sold by Silab under the name Helisun®; hesperitin laurate such as Flavagrum PEG® from the company Engelhard Lyon; an extract of Paeonia sujfruticosa root, such as the product sold by the company Ichimaru Pharcos under the name Botanpi Liquid B®; an extract of lychee such as the extract of lychee pericarp sold by the company Cognis under the name Litchiderm LS 9704®; an extract of pomegranate fruit (Punica granatum), such as the product sold by the company Draco Natural Products.

An antioxidant complex comprising vitamins C and E, and at least one carotenoid, especially a carotenoid chosen from β-carotene, lycopene, astaxanthin, zeaxanthin and lutein, flavonoids such as catechins, extract of pomegranate, hesperidin, neohesperidin, proanthocyanidins and anthocyanins, may also be used.

Such antioxidants may be present in a composition in accordance with the invention in a content of between 0.01% and 20% by weight, preferably between 0.05% and 10% by weight and preferentially between 0.05% and 5% by weight relative to the total weight of the composition.

The additional agent may also be at least one prebiotic or a mixture of prebiotics. More particularly, these prebiotics may be chosen from oligosaccharides, produced from glucose, galactose, xylose, maltose, sucrose, lactose, starch, xylan, hemicellulose, inulin, gums of acacia type, for example, or a mixture thereof.

More particularly, the oligosaccharide comprises at least one fructo- oligosaccharide. More particularly, this prebiotic may comprise a mixture of fructo- oligosaccharide and of inulin.

In the topical galenical forms, it is more particularly possible to use as hydrophilic agents proteins or protein hydrolysates, amino acids, polyols, especially of C₂ to C₁₀, for instance glycerol, sorbitol, butylene glycol or polyethylene glycol, urea, allantoin, sugars and sugar derivatives, water-soluble vitamins, starch, and bacterial or plant extracts, for instance those from Aloe vera.

As regards the lipophilic agents, retinol (vitamin A) and derivatives thereof, tocopherol (vitamin E) and derivatives thereof, ceramides, essential oils and unsaponifiable materials (tocotrienol, sesamine, gamma-oryzanol, phytosterols, squalenes, waxes and terpenes) may be used.

It is also advantageously possible to combine the product with agents that are capable of acting: - either directly on desquamation by promoting exfoliation, such as β-hydroxy acids, in particular salicylic acid and derivatives thereof (including 5-n-octanoylsalicylic acid); a- hydroxy acids, such as glycolic acid, citric acid, lactic acid, tartaric acid, malic acid or mandelic acid; urea and certain derivatives thereof; gentisic acid; oligofucoses; cinnamic acid; dioic acid, extract of Saphora japonica; resveratrol, detergents and certain jasmonic acid derivatives;

- and/or on the activities of enzymes involved in the degradation of corneodesmosomes, such as stratum corneum chymotryptic enzyme (SCCE), or even other proteases (trypsin-like, chymotryptic-like, cathepsin D) and also other categories of hydrolases (e.g.: glycosidases, ceramidases). Mention may be made of mineral salt chelating agents such as EDTA; N-acyl-N,N',N'-ethylenediaminetriacetic acid; aminosulfonic compounds and in particular (N-2-hydroxyethylpiperazine-N-2-ethane)sulfonic acid (HEPES); 2-oxothiazolidine-4-carboxylic acid (procysteine) derivatives; derivatives of alpha- amino acids of glycine type (as described in EP 0 852 949, and also sodium methyl glycine diacetate sold by BASF under the trade name Trilon M®); honey; sugar derivatives such as O-octanoyl-6-D-maltose and N-acetylglucosamine; urea or certain derivatives thereof, for example Hydrovance; C-glycoside derivatives.

Galenical form

The compositions according to the invention may be in any galenical form normally available for the selected mode of administration.

The support may be of diverse nature depending on the type of composition under consideration.

In the case of a parenteral use, the administration may take place via a patch.

Preferably, a parenteral administration corresponds to a topical administration.

The compositions intended for topical administration may be aqueous, aqueous- alcoholic or oily solutions, dispersions of the solution type or dispersions of the lotion or serum type, emulsions of liquid or semi-liquid consistency of the milk type, obtained by dispersing a fatty phase in an aqueous phase (O/W) or conversely (W/O), or a suspension or emulsion of soft, semi-solid or solid consistency, of the cream or aqueous or anhydrous gel type, microemulsions, microcapsules, microparticles, or vesicular dispersions of ionic and/or nonionic type. These compositions are prepared according to the usual methods.

They may be in the form of ointments, creams, milks, pomades, powders, impregnated pads, solutions, gels, sprays, lotions or suspensions.

These compositions may also constitute cleansing, peeling, treating or care creams for the face, the hands, the feet, the major anatomical folds or the body (for example day creams, night creams, makeup-removing creams, foundation creams or antisun creams), makeup products such as fluid foundations, makeup-removing milks, protective or care body milks, after-sun milks, skincare lotions, gels or mousses, for instance cleansing or disinfectant lotions, antisun lotions or artificial tanning lotions, bath compositions, deodorant compositions containing a bactericidal agent, aftershave gels or lotions, hair-removing creams, or compositions for combating insect stings. They may also be patches for local use.

The compositions according to the invention may also consist of solid preparations constituting soaps or cleansing bars.

The topical route advantageously makes it possible to deploy all the properties of the active agent according to the invention at a precise site, on the areas to be treated.

According to one preferred embodiment, a composition in accordance with the invention is in the form of a cream, a gel, a serum, a lotion or a milk for skincare and/or for removing makeup or an aftersun composition.

When the composition of the invention is an emulsion, the proportion of the fatty phase may range from 5% to 80% by weight and preferably from 5% to 50% by weight relative to the total weight of the composition. The oils, emulsifiers and coemulsifiers used in the composition in emulsion form are chosen from those conventionally used in cosmetics and/or dermatology. The emulsifier and the co-emulsifier may be present in the composition in a proportion ranging from 0.3% to 30% by weight and preferably from 0.5% to 20% by weight relative to the total weight of the composition.

When the composition of the invention is an oily solution or gel, the fatty phase may represent more than 90% of the total weight of the composition.

In a known manner, galenical forms intended for topical administration may also contain adjuvants that are common in the cosmetic, pharmaceutical and/or dermatological field, such as hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic agents, preserving agents, antioxidants, solvents, fragrances, fillers, screening agents, bactericides, odour absorbers and dyestuffs. The amounts of these various adjuvants are those conventionally used in the field under consideration, for example from 0.01% to 20% of the total weight of the composition. Depending on their nature, these adjuvants may be introduced into the fatty phase and/or into the aqueous phase.

As fatty substances that may be used in the invention, mention may be made of mineral oils, for instance hydrogenated polyisobutene and liquid petroleum jelly, plant oils, for instance a liquid fraction of shea butter, sunflower oil and apricot kernel oil, animal oils, for instance perhydrosqualene, synthetic oils, especially purcellin oil, isopropyl myristate and ethylhexyl palmitate, unsaturated fatty acids and fluoro oils, for instance perfluoropolyethers. It is also possible to use fatty alcohols, fatty acids, for instance stearic acid, and, for example, waxes, especially paraffin wax, carnauba wax and beeswax. It is also possible to use silicone compounds, for instance silicone oils and for example cyclomethicone and dimethicone, and silicone waxes, resins and gums.

As emulsifiers that may be used in the invention, mention may be made, for example, of glyceryl stearate, polysorbate 60, the mixture of cetylstearyl alcohol/cetylstearyl alcohol oxyethylenated with 33 mol of ethylene oxide sold under the name Sinnowax AO® by the company Henkel, the mixture of PEG-6/PEG-32/glycol stearate sold under the name Tefose® 63 by the company Gattefosse, PPG-3 myristyl ether, silicone emulsifiers such as cetyl dimethicone copolyol, and sorbitan monostearate or tristearate, PEG-40 stearate and oxyethylenated (20 EO) sorbitan monostearate.

As solvents that may be used in the invention, mention may be made of lower alcohols, for instance ethanol, isopropanol and propylene glycol.

According to one embodiment, a composition according to the invention may comprise from 10% to 80%> by weight of water, preferably from 20%> to 70%> by weight of water and preferentially from 30% to 60% by weight of water relative to the total weight of the composition.

This water may advantageously be a spring and/or mineral water, chosen especially from Vittel water, waters from the Vichy basin and la Roche Posay water.

Hydrophilic gelling agents that may be mentioned include carboxylic polymers such as carbomer, acrylic copolymers such as acrylate/alkyl acrylate copolymers, polyacrylamides and especially the mixture of polyacrylamide, C13-14 isoparaffin and laureth-7 sold under the name Sepigel 305® by the company SEPPIC, polysaccharides, for instance cellulose derivatives such as hydroxyalkyl celluloses and in particular hydroxypropyl cellulose and hydroxyethyl cellulose, natural gums such as guar gum, locust bean gum and xanthan gum, and clays. Lipophilic gelling agents that may be mentioned include modified clays, for instance bentones, metal salts of fatty acids, for instance aluminium stearates and hydrophobic silica, or else ethyl cellulose and polyethylene.

In the case of an oral use, the support is ingestible.

The ingestible support may be of diverse nature depending on the type of composition under consideration.

Milk, yoghurt, cheese, fermented milks, milk-based fermented products, ice creams, products based on fermented cereals, milk-based powders, baby and infant formulations, food products of candy type, chocolate, cereals, animal feed and in particular pet food, tablets, gel capsules or lozenges, oral supplements in dry form and oral supplements in liquid form are especially suitable for use as pharmaceutical or food supports.

The active agent according to the invention may moreover be formulated with the usual excipients and components for such oral compositions or food supplements, i.e. especially fatty and/or aqueous components, humectants, thickeners, preserving agents, texture agents, taste agents and/or coating agents, antioxidants, preserving agents and dyes that are common in the food sector.

The formulating agents and excipients for oral compositions, and especially for food supplements, are known in this field and will not be the subject of a detailed description herein.

For ingestion, numerous embodiments of oral compositions and especially of food supplements are possible. They are formulated via usual processes for producing coated tablets, gel capsules, gels, controlled-release hydrogels, emulsions, tablets and capsules.

In particular, the active agent according to the invention may be incorporated into any form of food supplement or enriched food, for example food bars, or compacted or loose powders. The powders may be diluted with water, in soda, dairy products or soybean derivatives, or may be incorporated into food bars.

In particular, the composition according to the invention may be a food composition for human consumption. This may be, in particular, nutritional complete foods, drinks, mineral waters, soups, dietary supplements and food replacement supplements, nutritional bars, confectionery, milk-based products or fermented milk-based products, yoghurts, milk-based powders, enteral nutritional products, infant and/or baby compositions, cereal-based products or fermented cereal-based products, ice creams, chocolate, coffee, "culinary" products such as mayonnaise, tomato puree or salad dressings. The composition according to the invention may also be intended for animals.

Cosmetic treatment process

As indicated previously, a process according to the invention may be performed by oral and/or parenteral, especially topical, application of an effective amount of at least one active agent consisting of a polypeptide having at least 80% amino acid identity with the metalloprotease MMP-12 whose sequence is chosen from SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, or a C-terminal fragment of the said polypeptide as defined previously, for treating and/or preventing greasy skin or greasy-prone skin and the associated skin disorders, especially aesthetic disorders, in an individual.

According to a preferred embodiment of the invention, this process is characterized in that the effective amount of at least one active agent according to the invention is used in a composition in accordance with the invention.

According to a preferred embodiment, the process may be performed by application of creams, gels, sera, lotions or milks for removing makeup or aftersun compositions to the skin, as regards topical application.

A topical cosmetic process of the invention may be performed, for example, on a daily basis, for instance at a rate of one administration per day or one administration twice a day, for example once in the morning and once in the evening.

A cosmetic process according to the invention may be performed over a time period ranging from one week to several weeks, or even several months, this period moreover possibly being repeated after periods without treatment, for several months or even several years.

By way of example, the topical administration of a compound according to the invention may be repeated, for example two to three times daily over one day or more and generally over an extended period of at least 4 weeks, with, where appropriate, one or more periods of stoppage.

Furthermore, treatment combinations optionally with oral or topical forms may be envisioned, in order to complement or to reinforce the activity of the active agent according to the invention as defined previously.

Thus, a topical treatment with a composition containing the active agent according to the invention combined with at least one or oral or topical composition optionally containing an anti-seborrhoeic agent different from the active agent according to the invention may be imagined.

The present invention discloses the use of an effective amount of at least one polypeptide having at least 80% amino acid identity with the metalloprotease MMP-12 whose sequence is chosen from SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, or a C-terminal fragment of this polypeptide, the said polypeptide or the said fragment comprising the sequence KDXK, in which X represents aspartic acid or glutamic acid, for the preparation of a pharmaceutical or dermato logical composition for preventing and/or treating skin infections with Malassezia sp, Propionibacterium acnes and/or Propionibacterium granulosum.

The present invention relates to the use of an effective amount of at least one polypeptide having at least 80% amino acid identity with the metalloprotease MMP-12 whose sequence is chosen from SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, or a C-terminal fragment of this polypeptide, the said polypeptide or the said fragment comprising the sequence KDXK, in which X represents aspartic acid or glutamic acid, for the preparation of a cosmetic or pharmaceutical composition for the topical application or the oral and/or parenteral administration for preventing and/or treating greasy skin or greasy-prone skin and/or a shiny complexion and/or acneic skin, which may or may not have imperfections on the facial skin.

According to one embodiment, the invention also discloses the use of an effective amount of at least one active agent in accordance with the invention for the preparation of a composition, especially a dermatological composition, for preventing and/or treating greasy skin or greasy-prone skin and the associated disorders, for instance dermatoses, especially of seborrhoeic type, and in particular acne.

The invention in particular discloses the use of an effective amount of at least one active agent for the preparation of a composition, especially a dermatological composition, for treating or preventing acne, in particular comedonal acne, papulo-pustular and/or nodular acne, acne conglobata and exogenous acne.

Such dermatoses may be benign complaints caused by excessive proliferation of a fungus and/or yeast especially a yeast of the genus Malassezia. The present invention also relates to the cosmetic use of an effective amount of at least one active agent in accordance with the invention for maintaining and/or restoring the homeostasis of the skin. In the description and the examples that follow, unless otherwise mentioned, the percentages are weight percentages and the ranges of values written in the form "between ... and ..." include the stated lower and upper limits.

The examples below are presented as non-limiting illustrations of the field of the invention.

EXAMPLES Compositions in accordance with the invention

Example 1 : face lotion

(weight%)

Polypeptide derived from MMP-12 (SEQ ID NO: 4) 5.00

Anti- inflammatory agent 0.05

Antioxidant 0.05

Isopropanol 40.0

Extracts of the alga Laminaria, Laminarghane^® 5.0

Preserving agent 0.30

Water qs 100

Example 2: Facial care milk

(weight%)

Polypeptide derived from MMP-12 (SEQ ID NO: 4) 5.00

Glyceryl stearate 1.00

Cetylstearyl oil/cetylstearyl oil oxyethylenated

with 30 mol OE (Sinnowax AO® sold by the company Henkel) 3.00

Cetyl alcohol 1.00

Dimethicone (DC 200 Fluid® sold by the company Dow Corning) 1.00

Liquid petroleum jelly 6.00

Isopropyl myristate (Estol® IMP 1514 sold by Unichema) 3.00

Antioxidant 0.05

Glycerol 20.00 Extracts of sugarcane Policosanol 2.50

Preserving agent 0.30

Water qs 100 Example 3 : Facial care gel

(weight%)

Polypeptide derived from MMP-12 (SEQ ID NO: 5) 5.00

Hydroxypropylcellulose (Klucel H® sold by the company Hercules) 1.00

Vitamin E 2.50 Antioxidant 0.05

Isopropanol 40.00

Preserving agent 0.30

Water qs 100 Example 4: Facial care milk

(weight%)

Polypeptide powder derived from MMP- 12 (SEQ ID NO : 4) 5.00

Glyceryl stearate 1.00 Cetylstearyl alcohol/cetylstearyl alcohol oxyethylenated

with 3 mol of OE (Sinnowax AO^® sold by the company Henkel) 3.00

Cetyl alcohol 1.00

Dimethicone (DC 200 Fluid^® sold by the company Dow Corning) 1.00

Liquid petroleum jelly 6.00

Isopropyl myristate (Estol IPM 1514^® sold by the company Unichema) 3.00 Glycerol 20.00

Preserving agent 0.30

Water qs 100

Example 5 : Facial care cream

(weight%)

Arachidyl behenyl alcohol/arachidyl glucoside 3.0

Isohexadecane 7.0

Polypeptide powder derived from MMP- 12 (SEQ ID NO : 4) 5.00 Glycerol 2.0

Vitreoscilla filiformis extract 3.0

BHT 0.05

Methyl POB 0.1

Propyl POB 0.05

Water qs 100

Example 6: Facial care gel

(weight%) Polypeptide powder derived from MMP- 12 (SEQ ID NO : 4) 5.00

Vitreoscilla filiformis extract 3.00

Antioxidant 0.05

Vitamin C 2.50

Isopropanol 40.00 Preserving agent 0.30

Water qs 100

Clinical study of compositions in accordance with the invention

In order to determine the antiacne effect of a topical treatment, on the face, of a composition A in accordance with the invention as defined below comprising a polypeptide derived from MMP- 12 (SEQ ID NO: 4), a double-lined randomized controlled comparative single-centre study was performed on two groups of 33 individuals each.

Composition A in accordance with the invention

Facial care cream

(weight%)

Arachidyl behenyl alcohol/arachidyl glucoside 3.0

Polypeptide powder derived from MMP- 12 (SEQ ID NO : 4) 5.00

Methyl POB 0.1

Propyl POB 0.05

Water qs 100 One of these two groups used a composition in accordance with the invention, namely the above composition, while the other group used only a placebo composition, identical to that used in the first group, except that it is free of active agent in accordance with the invention.

The individuals constituting these groups each applied to their face, daily for 61 days, the composition specific to the group to which they belonged.

After this period, a sensory evaluation of the efficacy of the test products on the imperfections and the condition of the facial skin was performed by means of scores (radiance, relief and condition of the skin). In addition, a self-evaluation of the radiance of the complexion and of the facial imperfections was performed.

Clinical evaluation

The main criterion for assessing the efficacy of the test compositions is defined by the number of superficial inflammatory lesions (papules and pustules, without distinction) and the number of retentional lesions (open and closed comedones, without distinction).

The counting is performed by an investigator at each consultation (Dl, D15, D29, D43 and D57) on the entire face (including the chin, but not the T area) by visual counting, according to the ECLA scale: Factor Fl : type and intensity of the acne on the whole face with scores from

0 to 5 (corresponding to counting of the lesions (0; <5; 5 to 9; 10 to 19; 20 to 40; >40))

- Non-inflamed lesions: Open or closed comedones with scores from 0 to 5 (corresponding to counting of the lesions (0; <5; 5 to 9; 10 to 19; 20 to 40; >40)).

- Inflamed lesions:

a) Superficial: papules and pustules with scores from 0 to 5 (corresponding to counting of the lesions (0; <5; 5 to 9; 10 to 19; 20 to 40; >40)),

b) Deep: nodules and cysts with scores from 0 to 5 (corresponding to counting of the lesions (0, 1, 2, 3, 4, 5)). Factor F2: extension and intensity of the acne beyond the face

- Neck with rating from 0 (absent) to 3 (pronounced) of the upper and lower cervical zone,

- Chest with rating from 0 (absent) to 3 (pronounced), - Back with rating from 0 (absent) to 3 (pronounced) (top point of the shoulder blade and bottom point of the shoulder blade),

- Arms with rating from 0 (absent) to 3 (pronounced). Factor F3 : scars

Absent (0) or present (1).

They may be inflammatory, non- inflammatory or excoriated.

Moreover, the investigator evaluates at each consultation (Dl, D15, D29, D43 and D57), on scales from 0 to 9:

• the presence of marks (freckles/actinic marks/depigmentation/beauty spots),

• witheredness,

• the presence of dartres,

• squamae,

· seborrhoeic dematitis.

Sensory evaluation

At each visit (Dl, D15, D29, D43 and D57), a trained jury of five people, the panellists, evaluate the radiance of the skin with the aid of unstructured scales (corresponding to scores ranging from 0 to 15):

• Skin colour (1):

Skin colour:

Red (skin colour): from very to not at all

Pink (skin colour): from not at all to very

Beige (skin colour): from not at all to very

Complexion uniformity: from not at all to very

Colour of the eye shadows from very dark to none

Redness/couperose: from pronounced to none • Skin relief (2):

Velvety skin: from not at all to very

Wrinkles/fine lines: from many to none

Fineness of the skin from coarse to fine

Bags (volume): from very swollen to none

• Skin condition (3):

Clearness of the complexion: from not at all to very

Skin radiance: from dull to radiant

Greasy skin - shininess of the skin: from very to not at all

The total score takes into account scores 1, 2 and 3 and gives an overall score of the radiance of the face.

Example of use of the scale:

Clearness of the complexion not at all very clear

The data are input directly by computer using the FIZZ® software.

Self-evaluation

At each visit (Dl , D15, D29, D43 and D57), the individuals evaluate the radiance of the complexion of their face on a scale of evaluation of the radiance of the complexion in which 0 denotes a dull complexion, 5 a complexion that is neither dull nor luminous, and 10 denotes a very luminous complexion.

In the course of the study (D15, D29, D43 and D57), the individuals evaluate the imperfections of their face on the following scales:

variation from the start of the treatment of the number of spots and of their redness, on the basis of the criteria: much fewer, fewer, identical, more or much more. variation from the start of the treatment of the number of blackheads, on the basis of the criteria: much fewer, fewer, identical, more or much more.

The efficacy of the test products on the level of sebaceous excretion was also evaluated:

1. Measurement of the seborrhoea on the forehead by sebumetry

The amount of sebum excreted at the surface of the skin is evaluated using a sebumeter^® (Courage & Khazaka).

This is a photometric method. A strip of synthetic material, which becomes transparent on contact with the absorbed lipids, is applied to the measurement area for precisely 30 seconds.

Its transparency then increases proportionally with the amount of sebum of the hydro lipid film with which it is in contact.

A recording by reflectometry makes it possible to quantify the increase in transmitted light and thus to determine the total mass of lipids excreted per unit of surface area (in μg.cm^"2).

A measurement on the forehead after careful defatting with 70° alcohol is performed.

30 minutes later, a new measurement is taken. The amount of sebum excreted per unit of surface area and per unit of time may thus be calculated.

Finally, the individuals themselves evaluated the change in their quality of life on the basis of a quality of life questionnaire (Cardiff Acne Disability Index (CADI)) scale (Motley et al. Practical use of a disability index in the routine management of acne, Clin. Exp. Dermatol, 1992 Jan, 17(1), 1-3).

The CADI questionnaire is a specialized scale that makes it possible to measure the psychological impact of the acne lesions. It is a questionnaire simplified as 5 items of the ADI (Acne Disability Index).

The results obtained after this clinical evaluation and of the self-evaluations and the biometrological evaluation show that the topical treatment of the skin with an active agent in accordance with the invention leads, after two months of treatment, to a decrease in the acne on the face, which is reflected by an improvement in certain signs of the acne associated with the surface condition, such as a less greasy skin, the disappearance of imperfections, and lightening of the complexion, which becomes uniform, free of dyschromia and free of areas of dryness.

Human metalloprotease MMP-12 in its mature form {Homo sapiens) SEP ID NO: 1

GPVWRKHYITYRINNYTPDMNREDVDYAIRKAFQVWSNVTPLKFSKINTGMADILV

VFARGAHGDFHAFDGKGGILAHAFGPGSGIGGDAHFDEDEFWTTHSGGTNLFLTAV

HEIGHSLGLGHSSDPKAVMFPTYKYVDINTFRLSADDIRGIQSLYGDPKENQRLPNPD

NSEPALCDPNLSFDAVTTVGNKIFFFKDRFFWLKVSERPKTSVNLISSLWPTLPSGIEA

AYEIEARNQVFLFKDDKYWLISNLRPEPNYPKSIHSFGFPNFVKKIDAAVFNPRFYRT

YFFVDNQYWRYDERRQMMDPGYPKLITKNFQGIGPKIDAVFYSKNKYYYFFQGSNQ

FEYDFLLQRITKTLKSNSWFGC

Mouse metalloprotease MMP-12 (Mus musculus)

SEP ID NO: 2

RSRWMKRYLTYRIYNYTPDMKREDVDYIFQKAFQVWSDVTPLRFRKLHKDEADIMI

LFAFGAHGDFNYFDGKGGTLAHAFYPGPGIQGDAHFDEAETWTKSFQGTNLFLVAV

HELGHSLGLQHSNNPKSIMYPTYRYLNPSTFRLSADDIRNIQSLYGAPVKPPSLTKPSS

PPSTFCHQSLSFDAVTTVGEKIFFFKDWFFWWKLPGSPATNITSISSIWPSIPSGIQAAY

EIESRNQLFLFKDEKYWLINNLVPEPHYPRSIYSLGFSASVK VDAAVFDPLRQKVYF

FVDKHYWRYDVRQELMDPAYPKLISTHFPGIKPKIDAVLYFKRHYYIFQGAYQLEYD

PLFRRVTKTLKSTSWFGC

Rat metalloprotease MMP-12 in its mature form (Rattus norvegicus)

SEP ID NP: 3

RSRWMKRYLTYRIYNYTPDMKRADVDYIFQKAFQVWSDVTPLRFRKIHKGEADITIL

FAFGDHGDFYDFDGKGGTLAHAFYPGPGIQGDAHFDEAETWTKSFQGTNLFLVAVH

ELGHSLGLPHSNNPKSIMYPTYRYLHPNTFRLSADDIHSIQSLYGAPVKNPSLTNPGSP

PSTVCHQSLSFDAVTTVGDKIFFFKDWFFWWRLPGSPATNITSISSMWPTIPSGIQAAY

EIGGRNQLFLFKDEKYWLINNLVPEPHYPRSIHSLGFPASVKKIDAAVFDPLRQKVYF

FVDKQYWRYDVRQELMDAAYPKLISTHFPGIRPKIDAVLYFKRHYYIFQGAYQLEYD

PLLHRVTKTLSSTSWFGC Peptide derived from Homo sapiens MMP-12 SEP ID NO: 4: ARNQVFLFKDDKYWLISNLR Peptide derived from Mus musculus MMP-12 SEP ID NP: 5: GRNQLFLFKDEKYWLINNLV Peptide derived from Rattus norvegicus MMP-12

SEP ID NP: 6: SRNQLFLFKDEKYWLINNLV

Claims

1. Cosmetic use of an effective amount of at least one active agent consisting of a polypeptide having at least 80% amino acid identity with a metalloprotease MMP-12 whose sequence is chosen from SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3 indicated below, or a C-terminal fragment of this polypeptide, for preventing and/or treating greasy skin and/or greasy-prone skin, the said polypeptide or the said fragment comprising the sequence KDXK, in which X represents aspartic acid or glutamic acid.

2. Use according to Claim 1, characterized in that the active agent used is a C- terminal fraction of the said polypeptide, with a length of 80 to 20 amino acids, preferably 50 to 20 amino acids and preferentially from 30 to 20 amino acids and comprising the sequence KDXK, in which X represents aspartic acid or glutamic acid.

3. Use according to either of Claims 1 and 2, characterized in that the active agent used according to the present invention is chosen from the sequences SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6.

4. Polypeptide with at least 80% amino acid identity with the metalloprotease MMP- 12 whose sequence is chosen from SEQ ID NO: 1 , SEQ ID NO: 2 and SEQ ID NO: 3, or a C- terminal fragment of the said polypeptide, for its use as an active agent in a pharmaceutical or dermato logical composition for preventing and/or treating skin infections caused by Malassezia furfur, Propionibacterium acnes and/or Propionibacterium granulosum, the said polypeptide or the said fragment comprising the sequence KDXK, in which X represents aspartic acid or glutamic acid.

5. Cosmetic and/or dermato logical composition for preventing and/or treating greasy skin or greasy-prone skin and the associated aesthetic disorders, comprising, in a physiologically acceptable medium, at least one active agent as defined in Claims 1 to 3, in combination with an effective amount of at least one additional anti-seborrhoeic agent other than the active agent as defined according to any one of Claims 1 to 3.

6. Composition according to the preceding claim, characterized in that the active agent as defined in Claims 1 to 3 is used in an amount of between 0.0001% and 30% by weight, preferably between 0.001% and 15% by weight and preferentially between 0.1 % and 10% by weight, relative to the total weight of the composition.

7. Composition according to either of Claims 5 and 6, characterized in that it is intended to be used orally and/or parenterally, preferably topically.

8. Composition according to any one of Claims 5 to 7, characterized in that the said additional anti-seborrhoeic agent is present in an amount of between 0.01% and 20% by weight, preferably between 0.1 % and 10%> by weight and preferentially between 0.1 % and 5% by weight, relative to the total weight of the composition.

9. Composition according to any one of Claims 5 to 8, characterized in that the said composition also comprises at least one fatty phase, preferably in a content ranging from 5% to 80% by weight and preferentially from 5% to 50% by weight, relative to the total weight of the composition.

10. Composition according to any one of Claims 5 to 9, characterized in that it comprises from 10%> to 80%> by weight of water, preferably from 20%> to 70%> by weight of water and preferentially from 30% to 60% by weight of water, relative to the total weight of the composition.

11. Composition according to any one of Claims 5 to 10, characterized in that it is in the form of a cream, a gel, a serum, a lotion or a milk for skincare and/or for removing makeup or an aftersun composition.

12. Cosmetic process for treating and/or preventing greasy skin or greasy-prone skin and the associated skin disorders in an individual, comprising at least one step of administering to the said individual at least an effective amount of at least one active agent as defined in any one of Claims 1 to 3.

13. Process according to Claim 12, characterized in that it is used orally and/or parenterally, preferably topically.

14. Process according to either of Claims 12 and 13, characterized in that the said effective amount of at least one active agent as defined in any one of Claims 1 to 3 is used in a composition as defined in any one of Claims 5 to 11.