WO2002047654A2 - Cosmetic composition comprising heparanase - Google Patents
Cosmetic composition comprising heparanase Download PDFInfo
- Publication number
- WO2002047654A2 WO2002047654A2 PCT/FR2001/003936 FR0103936W WO0247654A2 WO 2002047654 A2 WO2002047654 A2 WO 2002047654A2 FR 0103936 W FR0103936 W FR 0103936W WO 0247654 A2 WO0247654 A2 WO 0247654A2
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- WIPO (PCT)
- Prior art keywords
- composition
- polypeptide
- heparanase
- family
- intended
- Prior art date
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- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000012178 vegetable wax Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/007—Preparations for dry skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
- A61K8/66—Enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q7/00—Preparations for affecting hair growth
Definitions
- Cosmetic composition comprising heparanase
- the subject of the invention is a cosmetic composition comprising at least heparanase.
- the invention also relates to the uses of heparanase in a composition or for the preparation of a composition for the skin and / or the hair, as well as to a method of cosmetic treatment of the skin and / or the hair.
- Heparin sulfate and heparan sulfide proteoglycans are present in the extracellular matrix as well as on the outer surface of cells. Heparin sulfate and heparan sulfide proteoglycans play an important role in cell-cell and cell-extracellular matrix interactions.
- PGHSs are known to keep a large number of molecules with a biological effect, including growth factors, cytokines and enzymes.
- the hydrolysis of heparan sulfate can then lead to consequences on a large number of biological processes such as, for example, cell proliferation, cell differentiation or chemotactic displacement of cells, reshaping of extracellular matrices, angiogenesis.
- Hepananase is an endo- » -D-glucuronidase capable of hydrolyzing the glycosaminoglycan units of PGHS.
- Heparanase is known to be expressed and secreted among others by platelets, neutrophils, or even metastatic cells. It has also been found in fibroblasts.
- heparanase is also expressed in the skin, particularly the epidermis, very precisely in the stratum corneum, in mammals but particularly in humans. This suggests that heparanase may play a role in a large number of biological phenomena of the skin such as for example the desquamation by hydrolysis of intercellular PGHS, the modulation of hydration and of the osmotic status of the epidermis by release of sugar chains.
- composition for cosmetic use comprising at least one polypeptide from the heparanase family.
- the polypeptide of the invention is particularly human heparanase.
- a subject of the invention is also a composition for cosmetic use comprising a heparanase precursor.
- the heparanase of the invention is preferably functional heparanase.
- functional heparanase is meant here a heparanase capable of expressing at least one of the functions which are known to it in vivo.
- the primary amino acid sequence of a polypeptide determines sites specifically recognized by proteases which, once recognition of these sites is effective, will, with or without attachment to said polypeptide, induce its cleavage by proteolysis.
- the invention also relates to a composition for cosmetic use comprising at least one mixture of polypeptides derived from the proteolysis of at least one polypeptide from the heparanase family.
- the invention also relates to a composition for cosmetic use comprising at least one mixture of polypeptides resulting from the hydrolysis of at least one polypeptide of the heparanase family.
- the heparanase of the invention can be of natural or synthetic origin.
- natural origin is meant a polypeptide of the heparanase family in the pure state or in solution at different concentrations, obtained by different extraction methods from an organ (skin, liver, kidney, etc.) of natural origin.
- synthetic origin is meant a polypeptide of the heparanase family in the pure state or in solution at different concentrations, obtained chemically or by production in an organism after introduction into this organism of the elements necessary for this production.
- the heparanase of the invention is preferably of synthetic origin, obtained by genetic engineering from the sequence of human heparanase referenced AF084467 or Q9Y251.
- heparanase of the invention when the heparanase of the invention is of synthetic origin, it can be a fusion polypeptide.
- the amount of heparanase which can be used according to the invention is clearly understood as a function of the desired effect and can therefore vary to a large extent.
- the polypeptide of the heparanase family in the pure state is in an amount representing from 10.6 % to 10% of the total weight of the composition and preferably in an amount representing from 0.1% to 1% of the total weight of the composition.
- a subject of the invention is also the use in a composition or for the preparation of a composition, in a physiologically acceptable medium, of at least one polypeptide of the heparanase family as described above, the polypeptide or the composition being intended to favor the desquamation, to modulate the hydration of the skin, to modulate the osmotic status of the skin, to stimulate the antimicrobial defenses of the skin, to stimulate the immune defenses of the skin, to modulate the cellular differentiation at the level of the skin, particularly of the epidermis, to modulate cell renewal in the skin, particularly in the epidermis, to modulate the proliferation of skin cells, particularly of epidermis cells, to modulate the homeostasis of skin cells, particularly of the epidermis, to modulate hair growth and / or body hair.
- composition of the invention using a polypeptide from the heparanase family can be a composition for cosmetic or pharmaceutical use.
- the polypeptide of the heparanase family is used in a composition for cosmetic use.
- the composition of the invention can be administered parenterally, enterally or even topically.
- the composition is administered topically.
- composition of the invention is a cosmetic composition administered topically.
- compositions according to the invention can be presented in all the galenical forms normally used.
- the composition may have the form in particular of an aqueous or oily solution or of a dispersion of the lotion or serum type, of emulsions of liquid or semi-liquid consistency of the milk type, obtained by dispersion of a fatty phase in an aqueous phase (O / W) or vice versa (E / H), or suspensions or emulsions of soft consistency of the aqueous or anhydrous cream or gel type, or of microcapsules or microparticles, or of vesicular dispersions of the ionic and / or nonionic type or of foams or also in the form of compositions for aerosol also comprising a propellant under pressure.
- These compositions are prepared according to the usual methods.
- the composition may be in the form of an aqueous, oily lotion or in the form of a serum.
- the eyes it can be in the form of drops and for ingestion, it can be in the form of capsules, granules, syrups or tablets.
- compositions according to the invention are those conventionally used in the fields considered.
- compositions constitute in particular cleansing, protective, treatment or care creams for the face, for the hands, for the feet, for large anatomical folds or for the body (for example day creams, night creams, creams make-up removers, foundation creams, sunscreen creams), fluid foundations, make-up removal milks, body protection or care milks, anti-sun milks, after-sun milks, lotions, gels or skin care foams, such as cleansing lotions, sunscreen lotions, after sun lotions, artificial tanning lotions, bath compositions, deodorant compositions comprising a bactericidal agent, gels or aftershave lotions, depilatory creams, insect bite compositions, pain relieving compositions, compositions for treating certain skin conditions such as eczema, rosacea, psoriasis, s lichens, severe pruritus, ichthyosis.
- the compositions according to the invention may also consist of solid preparations constituting soaps or cleaning bars.
- compositions can also be packaged in the form of an aerosol composition also comprising a propellant under pressure.
- the composition according to the invention can also be a composition for the care of the scalp, and in particular a shampoo, a styling lotion, a treating lotion, a styling cream or gel, a composition of dyes (in particular dyes of oxidation) possibly in the form of coloring shampoos, restructuring hair lotions, a perm composition (in particular a composition for the first time of a perm), a fall prevention lotion or gel, an antiparasitic shampoo, the anti-dandruff compositions, etc. .
- the composition can also be for oral use, for example a toothpaste.
- the composition may contain adjuvants and additives customary for compositions for oral use and in particular surfactants, thickening agents, humectants, polishing agents such as silica, various active ingredients such as fluorides, in particular particularly sodium fluoride, and optionally sweetening agents such as sodium saccharinate.
- the proportion of the fatty phase can 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, waxes, emulsifiers and coemulsifiers used in the composition in the form of an emulsion are chosen from those conventionally used in the cosmetic field.
- the emulsifier and the coemulsifier are 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.
- the emulsion may, in addition, contain lipid vesicles.
- the fatty phase may represent more than 90% of the total weight of the composition.
- the cosmetic composition can also contain adjuvants customary in the cosmetic field, such as hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic additives, preservatives, antioxidants, solvents, perfumes, fillers, filters , odor absorbers and coloring matter.
- adjuvants customary in the cosmetic field such as hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic additives, preservatives, antioxidants, solvents, perfumes, fillers, filters , odor absorbers and coloring matter.
- the amounts of these various adjuvants are those conventionally used in the cosmetic field, and for example from 0.01% to 10% of the total weight of the composition.
- These adjuvants depending on their nature, can be introduced into the fatty phase, into the aqueous phase and / or into the lipid spherules.
- emulsifiers which can be used in the invention, there may be mentioned, for example, glycerol stearate, polysorbate 60 and the mixture of PEG-6 / PEG-32 / Glycol Stearate sold under the name Tefose ⁇ 63 by the company Gattefosse.
- solvents which can be used in the invention mention may be made of lower alcohols, in particular ethanol and isopropanol, propylene glycol.
- hydrophilic gelling agents which can be used in the invention, mention may be made of carboxyvinyl polymers (carbomer), acrylic copolymers such as acrylate / alkylacrylate copolymers, polyacrylamides, polysaccharides such as hydroxypropylcellulose, natural gums and clays, and, as lipophilic gelling agents, mention may be made of modified clays such as bentones, metal salts of fatty acids such as aluminum stearates and hydrophobic silica, ethylcellulose, polyethylene.
- the composition of the invention may comprise, in addition to the polypeptide of the heparanase family, any active ingredient useful in cosmetics.
- the present invention further relates to a method of cosmetic treatment of the skin and / or hair intended to promote desquamation, to modulate the hydration of the skin, to modulate the osmotic status of the skin, to stimulate the antimicrobial defenses of the skin, to stimulate the immune defenses of the skin, to modulate cell differentiation in the skin, particularly in the epidermis, in modulating cell renewal in the skin, particularly in the epidermis, to modulate the proliferation of skin cells, particularly of the epidermis, to modulate the homeostasis of the skin cells particularly of the epidermis, to modulate the growth of the hair and / or of the hairs.
- the treatment method of the invention is a cosmetic treatment method because it has no other purpose than to improve the aesthetics of the individual to whom it is applied.
- the cosmetic treatment process of the invention can be implemented in particular by applying the cosmetic compositions as defined above, according to the technique of usual use of these compositions. For example: application of creams, gels, serums, lotions, milks, shampoos or sunscreen compositions, on the skin or on the hair or on the hairs or also application of toothpaste on the gums and so preferable by oral administration of an oral solution, a syrup, a tablet, a capsule, a capsule or a nutritional food or nutritional supplement.
- heparanase is a protein naturally present in the skin, particularly in the epidermis, it should be considered that there are modulators of its expression. In some cases, it may be necessary either to stimulate or to decrease the expression of heparanase.
- the subject of the invention is also a composition comprising the combination of at least at least one polypeptide of the heparanase family and at least one modulator of the expression of said polypeptide, said modulator possibly being an activator or an inhibitor of the expression of heparanase.
- expression modulator is meant any element capable of increasing or decreasing the amount of heparanase, either by stimulating or by suppressing the synthesis of heparanase, whether by a transcriptional, post-transcriptional, translational or post translational, either by stimulating or suppressing the catabolism of heparanase, or by stimulating or repressing the intrinsic activity of heparanase.
- inhibitors of heparanase expression include free heparan sulfate, sugars released by the action of heparanase, trachyspic acid, suramin, non-anticoagulant derivatives heparin.
- compositions illustrate the invention without limiting it in any way.
- proportions indicated are percentages by weight.
- Example 1 Demonstration of the presence of a heparanase-like activity in the human epidermis.
- buffer A The mixture is ground with polytron (Bioblock) in a beaker placed in crushed ice. The extract is collected and centrifuged for 10 min. at 10,000g at
- a sample of Episkin TM type reconstructed epidermis (ER) is separated from its nacelle and placed in a potter. 500 ⁇ l of buffer A are added.
- the sample is ground in the pot on crushed ice.
- the extract is collected and centrifuged 10 min 10000g at 4 ° C.
- the supernatant is then filtered at
- the samples After incubation of the samples with heparan sulfate labeled with a fluorophore as described in the procedure by Toyoshima and Nakajima (Human heparanase, The Journal of Biological Chemistry, 2000, 274, 34, 24153-24160), the samples are diluted with Vz in Laemmli 2X buffer (Tris-HCI 0.125M pH 6.8, 4% SDS, 400mM DTT, 20% glycerol) and are subjected to an electrophoresis on SDS-PAGE 12.5% gel (Pharmacia). The fluorescence of the gel is observed with the Fluorimager (Molecular Dynamics).
- Example 2 Examples of formulations illustrating the invention. These compositions were obtained by simple mixing of the various components.
- Composition 1 Daily fall protection lotion:
- Composition 2 CARE CREAM:
- Cetarylgiucoside (sold under the name Montanov 68 by the company Seppic) 2.0%
- Aqueous phase Aqueous phase :
- the mode of preparation of the emulsion consists in mixing the oily phase in the aqueous phase at a temperature of approximately 70 ° C to 80 ° C while stirring with a turbine.
- the product obtained is an oil-in-water emulsion which has the appearance of a cream and can be used as a night cream to be applied daily.
- Composition 3 Cleansing gel with water
- the gel obtained has good cosmetic properties.
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- Life Sciences & Earth Sciences (AREA)
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- General Health & Medical Sciences (AREA)
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- Dermatology (AREA)
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Abstract
The invention concerns a cosmetic composition comprising at least heparanase. The invention also concerns the uses of heparanase in a composition or for preparing a composition for the skin and/or hair, and a cosmetic treatment method for the skin and/or hair.
Description
Composition cosmétique comprenant de l'héparanase Cosmetic composition comprising heparanase
L'invention a pour objet une composition cosmétique comprenant au moins de l'héparanase. L'invention se rapporte également aux utilisations de l'héparanase dans une composition ou pour la préparation d'une composition pour la peau et/ou les cheveux, ainsi qu'à un procédé de traitement cosmétique de la peau et/ou des cheveux.The subject of the invention is a cosmetic composition comprising at least heparanase. The invention also relates to the uses of heparanase in a composition or for the preparation of a composition for the skin and / or the hair, as well as to a method of cosmetic treatment of the skin and / or the hair.
L'héparane-sulfate et les protéoglycannes à héparane-suifate (PGHS) sont présents dans la matrice extracellulaire ainsi que sur la surface externe des cellules. L'héparane-sulfate et les protéoglycannes à héparane-suifate jouent un rôle important dans les interactions cellules-cellules et cellules-matrice extracellulaire.Heparin sulfate and heparan sulfide proteoglycans (PGHS) are present in the extracellular matrix as well as on the outer surface of cells. Heparin sulfate and heparan sulfide proteoglycans play an important role in cell-cell and cell-extracellular matrix interactions.
Les PGHS sont connus pour garder captives un grand nombre de molécules à effet biologique parmi lesquelles des facteurs de croissance, des cytokines et des enzymes. L'hydrolyse de l'héparane-sulfate peut alors entraîner des conséquences sur un grand nombre de processus biologiques comme par exemple la prolifération cellulaire, la différentiation cellulaire ou le déplacement chémotactique de cellules, le remodelage des matrices extracellulaires, f'angiogenèse.PGHSs are known to keep a large number of molecules with a biological effect, including growth factors, cytokines and enzymes. The hydrolysis of heparan sulfate can then lead to consequences on a large number of biological processes such as, for example, cell proliferation, cell differentiation or chemotactic displacement of cells, reshaping of extracellular matrices, angiogenesis.
L'héparanase est une endo-»-D-glucuronidase capable d'hydrolyser les unités glycosaminoglycannes des PGHS.Hepananase is an endo- » -D-glucuronidase capable of hydrolyzing the glycosaminoglycan units of PGHS.
L'héparanase est connu pour être exprimée et sécrétée entre autres par les plaquettes, les neutrophiles, ou encore les cellules métastatiques. Elle a également été retrouvée dans les fibroblastes.Heparanase is known to be expressed and secreted among others by platelets, neutrophils, or even metastatic cells. It has also been found in fibroblasts.
Le brevet US-5 968 822 décrit un polynucléotide codant pour un polypeptide correspondant à l'héparanase.US Pat. No. 5,968,822 describes a polynucleotide coding for a polypeptide corresponding to heparanase.
A la connaissance de la demanderesse, l'héparanase n'a jamais été décrite dans répiderme, particulièrement l'épiderme humain.To the knowledge of the applicant, heparanase has never been described in the epidermis, particularly the human epidermis.
La demanderesse vient maintenant de montrer que l'héparanase est également exprimée au niveau de la peau, particulièrement de l'épiderme, très précisément au niveau du stratum corneum, chez les mammifères mais
particulièrement chez l'être humain. Cela suggère que l'héparanase puisse jouer un rôle dans un grand nombre de phénomène biologique de la peau comme par exemple la desquamation par hydrolyse des PGHS intercellulaires, la modulation de l'hydratation et du statut osmotique de l'épiderme par libération de chaînes sucrées de bas poids moléculaire, la défense antimicrobienne de la peau par libération de chaînes sucrées de bas poids moléculaire, l'immunomodulation par action de l'héparanase au niveau des cellules de Langerhans "sensibilisées", la régulation de la différentiation et du renouvellement épidermique et la régulation de la prolifération épidermique par libération de facteurs tels que l'heparin-binding-EGF-like growth factor, les amphiregulines, le facteur de croissance épidermal (Epidermal Growth factor, EGF) à partir des PGHS ; la régulation de l'homéostasie épidermique par libération de facteurs à partir des PGHS tel que le facteur de croissance kéératinocytaire (KG F), ou de petites chaînes sucrées ; la régulation de la pousse du cheveu en agissant avec les facteurs de croissances, la fibronectine et les collagènes interstitiels.The Applicant has now shown that heparanase is also expressed in the skin, particularly the epidermis, very precisely in the stratum corneum, in mammals but particularly in humans. This suggests that heparanase may play a role in a large number of biological phenomena of the skin such as for example the desquamation by hydrolysis of intercellular PGHS, the modulation of hydration and of the osmotic status of the epidermis by release of sugar chains. of low molecular weight, the antimicrobial defense of the skin by release of low molecular weight sugar chains, immunomodulation by action of heparanase at the level of "sensitized" Langerhans cells, the regulation of differentiation and epidermal renewal and regulating epidermal proliferation by releasing factors such as heparin-binding-EGF-like growth factor, amphiregulins, epidermal growth factor (EGF) from PGHS; regulation of epidermal homeostasis by releasing factors from PGHS such as keratinocyte growth factor (KG F), or small sugar chains; regulation of hair growth by acting with growth factors, fibronectin and interstitial collagens.
La demanderesse propose alors une composition à usage cosmétique comprenant au moins un polypeptide de la famille des héparanases.The Applicant then proposes a composition for cosmetic use comprising at least one polypeptide from the heparanase family.
Le polypeptide de l'invention est particulièrement de l'héparanase humaine.The polypeptide of the invention is particularly human heparanase.
L'invention a également pour objet une composition à usage cosmétique comprenant un précurseur de l'héparanase.A subject of the invention is also a composition for cosmetic use comprising a heparanase precursor.
L'héparanase de l'invention est préférentiellement de l'héparanase fonctionnelle. Par heparanase fonctionnelle on entend ici une heparanase capable d'exprimer au moins une des fonctions qui lui sont connues in vivo.The heparanase of the invention is preferably functional heparanase. By functional heparanase is meant here a heparanase capable of expressing at least one of the functions which are known to it in vivo.
II est par ailleurs connu que la séquence primaire en acides aminés d'un polypeptide détermine des sites spécifiquement reconnus par des protéases qui une fois la reconnaissance de ces sites effective vont, avec ou sans fixation audit polypeptide, induire son clivage par protéolyse.
Ainsi, l'invention concerne également une composition à usage cosmétique comprenant au moins un mélange de polypeptides issus de la protéolyse d'au moins un polypeptide de la famille des héparanases.It is moreover known that the primary amino acid sequence of a polypeptide determines sites specifically recognized by proteases which, once recognition of these sites is effective, will, with or without attachment to said polypeptide, induce its cleavage by proteolysis. Thus, the invention also relates to a composition for cosmetic use comprising at least one mixture of polypeptides derived from the proteolysis of at least one polypeptide from the heparanase family.
L'invention concerne également une composition à usage cosmétique comprenant au moins un mélange de polypeptides issus de l'hydrolyse d'au moins un polypeptide de la famille des héparanases.The invention also relates to a composition for cosmetic use comprising at least one mixture of polypeptides resulting from the hydrolysis of at least one polypeptide of the heparanase family.
L'héparanase de l'invention peut être d'origine naturelle ou synthétique.The heparanase of the invention can be of natural or synthetic origin.
Par "origine naturelle", on entend un polypeptide de la famille des héparanases à l'état pur ou en solution à différentes concentrations, obtenu par différents procédés d'extraction à partir d'un organe (peau, foie, rein, etc.) d'origine naturelle.By "natural origin" is meant a polypeptide of the heparanase family in the pure state or in solution at different concentrations, obtained by different extraction methods from an organ (skin, liver, kidney, etc.) of natural origin.
Par "origine synthétique", on entend un polypeptide de la famille des héparanases à l'état pur ou en solution à différentes concentrations, obtenu chimiquement ou par production dans un organisme après introduction dans cet organisme des éléments nécessaires à cette production.By "synthetic origin" is meant a polypeptide of the heparanase family in the pure state or in solution at different concentrations, obtained chemically or by production in an organism after introduction into this organism of the elements necessary for this production.
L'héparanase de l'invention est préférentiellement d'origine synthétique, obtenu par génie génétique à partir de la séquence de l'héparanase humaine référencée AF084467 ou Q9Y251.The heparanase of the invention is preferably of synthetic origin, obtained by genetic engineering from the sequence of human heparanase referenced AF084467 or Q9Y251.
Lorsque l'héparanase de l'invention est d'origine synthétique elle peut être un polypeptide de fusion.When the heparanase of the invention is of synthetic origin, it can be a fusion polypeptide.
La quantité d'héparanase utilisable selon l'invention est bien entendue fonction de l'effet recherché et peut donc varier dans une large mesure.The amount of heparanase which can be used according to the invention is clearly understood as a function of the desired effect and can therefore vary to a large extent.
Pour donner un ordre de grandeur, dans la composition selon l'invention le polypeptide de la famille des héparanases à l'état pur est en une quantité représentant de 10"6% à 10% du poids total de la composition et
préférentiellement en une quantité représentant de 0,1% à 1% du poids total de la composition.To give an order of magnitude, in the composition according to the invention, the polypeptide of the heparanase family in the pure state is in an amount representing from 10.6 % to 10% of the total weight of the composition and preferably in an amount representing from 0.1% to 1% of the total weight of the composition.
L'invention a également pour objet l'utilisation dans une composition ou pour la préparation d'une composition, dans un milieu physiologiquement acceptable, d'au moins un polypeptide de la famille des héparanases tel que décrit précédemment, le polypeptide ou la composition étant destinés à favoriser la desquamation, à moduler l'hydratation de la peau, à moduler le statut osmotique de la peau, à stimuler les défenses antimicrobienne de la peau, à stimuler les défenses immunitaires de la peau, à moduler la différenciation cellulaire au niveau de la peau, particulièrement de l'épiderme, à moduler le renouvellement cellulaire au niveau de la peau, particulièrement au niveau de l'épiderme, à moduler la prolifération des cellules de la peau, particulièrement des cellules de l'épiderme, à moduler l'homéostasie des cellules de la peau particulièrement de l'épiderme, à moduler la pousse des cheveux et ou des poils.A subject of the invention is also the use in a composition or for the preparation of a composition, in a physiologically acceptable medium, of at least one polypeptide of the heparanase family as described above, the polypeptide or the composition being intended to favor the desquamation, to modulate the hydration of the skin, to modulate the osmotic status of the skin, to stimulate the antimicrobial defenses of the skin, to stimulate the immune defenses of the skin, to modulate the cellular differentiation at the level of the skin, particularly of the epidermis, to modulate cell renewal in the skin, particularly in the epidermis, to modulate the proliferation of skin cells, particularly of epidermis cells, to modulate the homeostasis of skin cells, particularly of the epidermis, to modulate hair growth and / or body hair.
La composition de l'invention utilisant un polypeptide de la famille des héparanases peut être une composition à usage cosmétique ou pharmaceutique.The composition of the invention using a polypeptide from the heparanase family can be a composition for cosmetic or pharmaceutical use.
De préférence selon l'invention, on utilise le polypeptide de la famille des héparanases dans une composition à usage cosmétique. La composition de l'invention peut être administrée par voie parentérale, entérale ou encore par voie topique. De préférence, la composition est administrée par voie topique.Preferably according to the invention, the polypeptide of the heparanase family is used in a composition for cosmetic use. The composition of the invention can be administered parenterally, enterally or even topically. Preferably, the composition is administered topically.
Très préférentiellement la composition de l'invention est une composition cosmétique administrée par voie topique.Very preferably the composition of the invention is a cosmetic composition administered topically.
Selon le mode d'administration, les compositions selon l'invention peuvent se présenter sous toutes les formes galéniques normalement utilisées.According to the mode of administration, the compositions according to the invention can be presented in all the galenical forms normally used.
Pour une application topique sur la peau, la composition peut avoir la forme
notamment de solution aqueuse ou huileuse ou de dispersion du type lotion ou sérum, d'émulsions de consistance liquide ou semi-liquide du type lait, obtenues par dispersion d'une phase grasse dans une phase aqueuse (H/E) ou inversement (E/H), ou de suspensions ou émulsions de consistance molle du type crème ou gel aqueux ou anhydres, ou encore de microcapsules ou microparticules, ou de dispersions vésiculaires de type ionique et/ou non ionique ou de mousses ou encore sous forme de compositions pour aérosol comprenant également un agent propulseur sous pression. Ces compositions sont préparées selon les méthodes usuelles.For topical application to the skin, the composition may have the form in particular of an aqueous or oily solution or of a dispersion of the lotion or serum type, of emulsions of liquid or semi-liquid consistency of the milk type, obtained by dispersion of a fatty phase in an aqueous phase (O / W) or vice versa (E / H), or suspensions or emulsions of soft consistency of the aqueous or anhydrous cream or gel type, or of microcapsules or microparticles, or of vesicular dispersions of the ionic and / or nonionic type or of foams or also in the form of compositions for aerosol also comprising a propellant under pressure. These compositions are prepared according to the usual methods.
Pour l'injection, la composition peut se présenter sous forme de lotion aqueuse, huileuse ou sous forme de sérum. Pour les yeux, elle peut se présenter sous forme de gouttes et pour l'ingestion, elle peut se présenter sous forme de capsules, de granulés, de sirops ou de comprimés.For injection, the composition may be in the form of an aqueous, oily lotion or in the form of a serum. For the eyes, it can be in the form of drops and for ingestion, it can be in the form of capsules, granules, syrups or tablets.
Les quantités des différents constituants des compositions selon l'invention sont celles classiquement utilisées dans les domaines considérés.The amounts of the various constituents of the compositions according to the invention are those conventionally used in the fields considered.
Ces compositions constituent notamment des crèmes de nettoyage, de protection, de traitement ou de soin pour le visage, pour les mains, pour les pieds, pour les grands plis anatomiques ou pour le corps (par exemple crèmes de jour, crèmes de nuit, crèmes démaquillantes, crèmes de fond de teint, crèmes anti-solaires), des fonds de teint fluides, des laits de démaquillage, des laits corporels de protection ou de soin, des laits anti-solaires, des laits après- soleil, des lotions, gels ou mousses pour le soin de la peau, comme des lotions de nettoyage, des lotions anti-solaires, des lotions après-soleil, des lotions de bronzage artificiel, des compositions pour le bain, des compositions désodorisantes comprenant un agent bactéricide, des gels ou lotions après- rasage, des crèmes épilatoires, des compositions contre les piqûres d'insectes, des compositions anti-douleur, des compositions pour traiter certaines maladies de la peau comme l'eczéma, la rosacée, le psoriasis, les lichens, les prurits sévères, l'ichthyose.
Les compositions selon l'invention peuvent également consister en des préparations solides constituant des savons ou des pains de nettoyage.These compositions constitute in particular cleansing, protective, treatment or care creams for the face, for the hands, for the feet, for large anatomical folds or for the body (for example day creams, night creams, creams make-up removers, foundation creams, sunscreen creams), fluid foundations, make-up removal milks, body protection or care milks, anti-sun milks, after-sun milks, lotions, gels or skin care foams, such as cleansing lotions, sunscreen lotions, after sun lotions, artificial tanning lotions, bath compositions, deodorant compositions comprising a bactericidal agent, gels or aftershave lotions, depilatory creams, insect bite compositions, pain relieving compositions, compositions for treating certain skin conditions such as eczema, rosacea, psoriasis, s lichens, severe pruritus, ichthyosis. The compositions according to the invention may also consist of solid preparations constituting soaps or cleaning bars.
Les compositions peuvent aussi être conditionnées sous forme de composition pour aérosol comprenant également un agent propulseur sous pression.The compositions can also be packaged in the form of an aerosol composition also comprising a propellant under pressure.
La composition selon l'invention peut aussi être une composition pour les soins du icuir chevelu, et notamment un shampooing, une lotion de mise en plis, une lotion traitante, une crème ou un gel coiffant, une composition de teintures (notamment teintures d'oxydation) éventuellement sous forme de shampooings colorants, des lotions restructurantes pour les cheveux, une composition de permanente (notamment une composition pour le premier temps d'une permanente), une lotion ou un gel antichute, un shampooing antiparasitaire, les compositions antipelliculaires, etc.The composition according to the invention can also be a composition for the care of the scalp, and in particular a shampoo, a styling lotion, a treating lotion, a styling cream or gel, a composition of dyes (in particular dyes of oxidation) possibly in the form of coloring shampoos, restructuring hair lotions, a perm composition (in particular a composition for the first time of a perm), a fall prevention lotion or gel, an antiparasitic shampoo, the anti-dandruff compositions, etc. .
La composition peut aussi être à usage bucco-dentaire, par exemple une pâte dentifrice. Dans ce cas, la composition peut contenir des adjuvants et additifs usuels pour les compositions à usage buccal et notamment des agents tensioactifs, des agents épaississants, des agents humectants, des agents de polissage tels que la silice, divers ingrédients actifs comme les fluorures, en particulier le fluorure de sodium, et éventuellement des agents édulcorants comme le saccharinate de sodium.The composition can also be for oral use, for example a toothpaste. In this case, the composition may contain adjuvants and additives customary for compositions for oral use and in particular surfactants, thickening agents, humectants, polishing agents such as silica, various active ingredients such as fluorides, in particular particularly sodium fluoride, and optionally sweetening agents such as sodium saccharinate.
Lorsque la composition est une émulsion, la proportion de la phase grasse peut aller de 5 % à 80 % en poids, et de préférence de 5 % à 50 % en poids par rapport au poids total de la composition. Les huiles, les cires, les émulsionnants et les coémulsionnants utilisés dans la composition sous forme d'émulsion sont choisis parmi ceux classiquement utilisés dans le domaine cosmétique. L'émulsionnant et le coémulsionnant sont présents, dans la composition, en une proportion allant de 0,3 % à 30 % en poids, et de préférence de 0,5 à 20 % en poids par rapport au poids total de la composition. L'émulsion peut, en outre, contenir des vésicules lipidiques. Lorsque la composition est une solution ou un gel huileux, la phase grasse
peut représenter plus de 90 % du poids total de la composition.When the composition is an emulsion, the proportion of the fatty phase can 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, waxes, emulsifiers and coemulsifiers used in the composition in the form of an emulsion are chosen from those conventionally used in the cosmetic field. The emulsifier and the coemulsifier are 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. The emulsion may, in addition, contain lipid vesicles. When the composition is an oily solution or gel, the fatty phase may represent more than 90% of the total weight of the composition.
De façon connue, la composition cosmétique peut contenir également des adjuvants habituels dans le domaine cosmétique, tels que les gélifiants' hydrophiles ou lipophiles, les additifs hydrophiles ou lipophiles, les conservateurs, les antioxydants, les solvants, les parfums, les charges, les filtres, les absorbeurs d'odeur et les matières colorantes. Les quantités de ces différents adjuvants sont celles classiquement utilisées dans le domaine cosmétique, et par exemple de 0,01 % à 10 % du poids total de la composition. Ces adjuvants, selon leur nature, peuvent être introduits dans la phase grasse, dans la phase aqueuse et/ou dans les sphérules lipidiques. Comme huiles ou cires utilisables dans l'invention, on peut citer les huiles minérales (huile de vaseline), les huiles végétales (fraction liquide du beurre de^ karité, huile de tournesol), les huiles animales (perhydrosqualène), les huiles de synthèse (huile de Purcellin), les huiles ou cires siliconées (cyclométhicone) et les huiles fluorées (perfluoropolyéthers), les cires d'abeille, de camauba ou paraffine. On peut ajouter à ces huiles des alcools gras et des acides gras (acide stéarique). Comme émulsionnants utilisables dans l'invention, on peut citer par exemple le stéarate de glycerol, le polysorbate 60 et le mélange de PEG-6/PEG-32/Glycol Stéarate vendu sous la dénomination de Tefose^ 63 par la société Gattefosse.In a known manner, the cosmetic composition can also contain adjuvants customary in the cosmetic field, such as hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic additives, preservatives, antioxidants, solvents, perfumes, fillers, filters , odor absorbers and coloring matter. The amounts of these various adjuvants are those conventionally used in the cosmetic field, and for example from 0.01% to 10% of the total weight of the composition. These adjuvants, depending on their nature, can be introduced into the fatty phase, into the aqueous phase and / or into the lipid spherules. As oils or waxes which can be used in the invention, mention may be made of mineral oils (petroleum jelly oil), vegetable oils (liquid fraction of shea butter, sunflower oil), animal oils (perhydrosqualene), synthetic oils (Purcellin oil), silicone oils or waxes (cyclomethicone) and fluorinated oils (perfluoropolyethers), beeswax, camauba or paraffin. Fatty alcohols and fatty acids (stearic acid) can be added to these oils. As emulsifiers which can be used in the invention, there may be mentioned, for example, glycerol stearate, polysorbate 60 and the mixture of PEG-6 / PEG-32 / Glycol Stearate sold under the name Tefose ^ 63 by the company Gattefosse.
Comme solvants utilisables dans l'invention, on peut citer les alcools inférieurs, notamment l'éthanol et l'isopropanol, le propylène glycol.As solvents which can be used in the invention, mention may be made of lower alcohols, in particular ethanol and isopropanol, propylene glycol.
Comme gélifiants hydrophiles utilisables dans l'invention, on peut citer les polymères carboxyvinyliques (carbomer), les copolymères acryliques tels que les copolymères d'acrylates/alkylacrylates, les polyacrylamides, les polysaccharides tels que l'hydroxypropylcellulose, les gommes naturelles et les argiles, et, comme gélifiants lipophiles, on peut citer les argiles modifiées comme les bentones, les sels métalliques d'acides gras comme les stéarates d'aluminium et la silice hydrophobe, éthylcellulose, polyéthylène.
Bien entendu, la composition de l'invention peut comprendre outre le polypeptide de la famille des héparanases, tout actif utile en cosmétique. La présente invention a en outre pour objet un procédé de traitement cosmétique de la peau et/ou des cheveux destiné à favoriser la desquamation, à moduler l'hydratation de la peau, à moduler le statut osmotique de la peau, à stimuler les défenses antimicrobienne de la peau, à stimuler les défenses immunitaires de la peau, à moduler la différenciation cellulaire au niveau de la peau, particulièrement de l'épiderme, à moduler le renouvellement cellulaire au niveau de la peau, particulièrement au niveau de l'épiderme, à moduler la prolifération des cellules de la peau, particulièrement des cellules de l'épiderme, à moduler l'homéostasie des cellules de la peau particulièrement de l'épiderme, à moduler la pousse des cheveux et/ou des poils.As hydrophilic gelling agents which can be used in the invention, mention may be made of carboxyvinyl polymers (carbomer), acrylic copolymers such as acrylate / alkylacrylate copolymers, polyacrylamides, polysaccharides such as hydroxypropylcellulose, natural gums and clays, and, as lipophilic gelling agents, mention may be made of modified clays such as bentones, metal salts of fatty acids such as aluminum stearates and hydrophobic silica, ethylcellulose, polyethylene. Of course, the composition of the invention may comprise, in addition to the polypeptide of the heparanase family, any active ingredient useful in cosmetics. The present invention further relates to a method of cosmetic treatment of the skin and / or hair intended to promote desquamation, to modulate the hydration of the skin, to modulate the osmotic status of the skin, to stimulate the antimicrobial defenses of the skin, to stimulate the immune defenses of the skin, to modulate cell differentiation in the skin, particularly in the epidermis, in modulating cell renewal in the skin, particularly in the epidermis, to modulate the proliferation of skin cells, particularly of the epidermis, to modulate the homeostasis of the skin cells particularly of the epidermis, to modulate the growth of the hair and / or of the hairs.
Le procédé de traitement de l'invention est un procédé de traitement cosmétique car il n'a d'autre but que d'améliorer l'esthétique de l'individu auquel il est appliqué.The treatment method of the invention is a cosmetic treatment method because it has no other purpose than to improve the aesthetics of the individual to whom it is applied.
Le procédé de traitement cosmétique de l'invention peut être mis en œuvre notamment en appliquant les compositions cosmétiques telles que définies ci-dessus, selon la technique d'utilisation habituelle de ces compositions. Par exemple : application de crèmes, de gels, de sérums, de lotions, de laits, de shampooings ou de compositions anti-solaires, sur la peau ou sur les cheveux ou sur les poils ou encore application de dentifrice sur les gencives et de manière préférentielle par administration par voie orale d'une solution buvable, d'un sirop, d'un comprimé, d'une gélule, d'une capsule ou encore un aliment nutritionnel ou d'un complément nutritionnel.The cosmetic treatment process of the invention can be implemented in particular by applying the cosmetic compositions as defined above, according to the technique of usual use of these compositions. For example: application of creams, gels, serums, lotions, milks, shampoos or sunscreen compositions, on the skin or on the hair or on the hairs or also application of toothpaste on the gums and so preferable by oral administration of an oral solution, a syrup, a tablet, a capsule, a capsule or a nutritional food or nutritional supplement.
Dans la mesure où l'héparanase est une protéine naturellement présente dans la peau, particulièrement dans l'épiderme, il faut envisager qu'il existe des modulateurs de son expression. Il peut s'avérer dans certains cas nécessaire soit de stimuler soit de diminuer l'expression de l'héparanase.Since heparanase is a protein naturally present in the skin, particularly in the epidermis, it should be considered that there are modulators of its expression. In some cases, it may be necessary either to stimulate or to decrease the expression of heparanase.
L'invention a encore pour objet une composition comprenant l'association d'au
moins un polypeptide de la famille des héparanases et d'au moins un modulateur de l'expression dudit polypeptide, ledit modulateur pouvant être un activateur ou un inhibiteur de l'expression de l'héparanase.The subject of the invention is also a composition comprising the combination of at least at least one polypeptide of the heparanase family and at least one modulator of the expression of said polypeptide, said modulator possibly being an activator or an inhibitor of the expression of heparanase.
Par modulateur de l'expression il faut entendre tout élément capable d'augmenter ou de diminuer la quantité d'héparanase, soit en stimulant soit en réprimant la synthèse de l'héparanase, que ce soit par un mécanisme transcriptionnel, post transcriptionnel, translationnel ou post translationnel, soit en stimulant soit en réprimant le catabolisme de l'héparanase, soit en stimulant soit en réprimant l'activité intrinsèque de l'héparanase.By expression modulator is meant any element capable of increasing or decreasing the amount of heparanase, either by stimulating or by suppressing the synthesis of heparanase, whether by a transcriptional, post-transcriptional, translational or post translational, either by stimulating or suppressing the catabolism of heparanase, or by stimulating or repressing the intrinsic activity of heparanase.
A titre d'exemple d'inhibiteurs de l'expression de l'héparanase, on peut citer l'héparane sulfate libre, les sucres libérés par l'action de l'héparanase, l'acide trachyspique, la suramine, les dérivés non anticoagulants de l'héparine.Examples of inhibitors of heparanase expression include free heparan sulfate, sugars released by the action of heparanase, trachyspic acid, suramin, non-anticoagulant derivatives heparin.
Les exemples et compositions suivants illustrent l'invention sans la limiter aucunement. Dans les compositions les proportions indiquées sont des pourcentages en poids.The following examples and compositions illustrate the invention without limiting it in any way. In the compositions the proportions indicated are percentages by weight.
Exemple 1 : Démonstration de la présence d'une activité de type heparanase dans l'épiderme humain.Example 1: Demonstration of the presence of a heparanase-like activity in the human epidermis.
Préparation des échantillons :Sample preparation:
Sur une pesée de 1 g de Stratum Corneum Plantaire, on ajoute 6 ml de tampon acétate de sodium 50 mM pH 4.2, 0.1% TX100, 150 mM NaCIOn a weighing of 1 g of Plantar Corneum Plantar, 6 ml of 50 mM sodium acetate buffer pH 4.2, 0.1% TX100, 150 mM NaCl are added.
(tampon A). Le mélange est broyé au polytron (Bioblock) dans un bêcher placé dans de la glace pilée. L'extrait est recueilli et centrifugé 10 min. à 10 000g à(buffer A). The mixture is ground with polytron (Bioblock) in a beaker placed in crushed ice. The extract is collected and centrifuged for 10 min. at 10,000g at
4°C. Le surnageant est alors filtré à 0.8 μm puis 0.22μm.4 ° C. The supernatant is then filtered at 0.8 μm then 0.22 μm.
Un échantillon d'épiderme reconstruit (ER) de type Episkin™ est séparé de sa nacelle et disposé dans un potter. 500 μl de tampon A sont ajoutés.A sample of Episkin ™ type reconstructed epidermis (ER) is separated from its nacelle and placed in a potter. 500 μl of buffer A are added.
L'échantillon est broyé dans le potter placé sur de la glace pilée. L'extrait est recueilli et centrifugé 10 min 10000g à 4°C. Le surnageant est alors filtré àThe sample is ground in the pot on crushed ice. The extract is collected and centrifuged 10 min 10000g at 4 ° C. The supernatant is then filtered at
0.8μm puis 0.22μm.
Electrophorèse des échantillons :0.8μm then 0.22μm. Electrophoresis of samples:
Après l'incubation des échantillons avec de l'héparane sulfate marqué par un fluorophore telle que décrite dans la procédure par Toyoshima et Nakajima (Human heparanase, The Journal of Biological Chemistry, 2000, 274, 34, 24153-24160), les échantillons sont dilués au Vz dans du tampon Laemmli 2X (Tris-HCI 0.125M pH 6.8, 4%SDS, 400mM DTT, 20% glycerol) et font l'objet d'une electrophorèse sur gel SDS-PAGE 12.5% (Pharmacia). La fluorescence du gel est observée avec le Fluorimager (Molecular Dynamics).After incubation of the samples with heparan sulfate labeled with a fluorophore as described in the procedure by Toyoshima and Nakajima (Human heparanase, The Journal of Biological Chemistry, 2000, 274, 34, 24153-24160), the samples are diluted with Vz in Laemmli 2X buffer (Tris-HCI 0.125M pH 6.8, 4% SDS, 400mM DTT, 20% glycerol) and are subjected to an electrophoresis on SDS-PAGE 12.5% gel (Pharmacia). The fluorescence of the gel is observed with the Fluorimager (Molecular Dynamics).
Résultats :Results:
Le décalage de la fluorescence de l'héparane sulfate vers des poids moléculaires plus bas permet de démontrer une activité heparanase dans les deux types d'échantillons épidermiques testés. L'activité de l'échantillon de Stratum Corneum plantaire étant la plus forte.The shift in the fluorescence of heparan sulfate to lower molecular weights makes it possible to demonstrate heparanase activity in the two types of epidermal samples tested. The activity of the plantar Stratum Corneum sample being the strongest.
2) Purification de l'héparanase à partir du Stratum Corneum Plantaire Humain.2) Purification of heparanase from the Human Plantar Stratum Corneum.
Préparation de l'échantillon :Sample preparation:
Sur une pesée de 100g de Stratum Corneum plantaire on ajoute 600 ml de tampon HEPES/KOH 10mM pH7.4, NaCI 150mM, 0.1% TritonX100 réduit. L'échantillon est ensuite homogénéisé à l'aide d'un Polytron (Bioblock) puis filtré sur macrofiltre nylon de maille 40μm. L'extrait est alors centrifugé àOn a weighing of 100 g of plantar Stratum Corneum, 600 ml of 10 mM HEPES / KOH buffer pH7.4, 150 mM NaCl, 0.1% reduced TritonX100 are added. The sample is then homogenized using a Polytron (Bioblock) and then filtered through a 40 μm nylon macrofilter. The extract is then centrifuged at
10000g pendant 10 min. Le surnageant est finalement filtré à 0.22μm.10000g for 10 min. The supernatant is finally filtered at 0.22 μm.
Purification :Purification:
La purification suit essentiellement la procédure décrite par Toyoshima et Nakajima. Seuls diffèrent la préparation et l'origine de l'échantillon ainsi que la colonne d'échange cationique utilisée qui est dans notre cas une colonneThe purification essentially follows the procedure described by Toyoshima and Nakajima. Only the preparation and the origin of the sample differ as well as the cation exchange column used which is in our case a column
UNOS6 (Biorad).UNOS6 (Biorad).
Séparation de l'héparanase et identification :Separation of heparanase and identification:
Les fractions récupérées après l'étape de chromatographie hydrophobe et contenant une activité heparanase sont mélangées et séparées par electrophorèse SDS-PAGE à 12.5% d'acrylamide. Une protéine majoritaire deThe fractions recovered after the hydrophobic chromatography step and containing heparanase activity are mixed and separated by SDS-PAGE electrophoresis with 12.5% acrylamide. A majority protein of
62 kD est visualisée sur le gel après coloration au bleu de Coomassie. Après digestion trypsique de la bande découpée dans le gel, un peptide séparé par
HPLC est séquence par la technique d'Edmann. La séquence suivante est obtenue : LRPGSSLGLPAFSYSFFVIRNAK. Cette séquence présence une homologie de 100% avec l'héparanase Humaine qui est référencée dans les bases de données IDQ9UL39 (Dempsey and al. 08/98) ou IDQ9Y251 (Vlodavsky et al. 04/99).62 kD is visualized on the gel after staining with Coomassie blue. After tryptic digestion of the strip cut from the gel, a peptide separated by HPLC is sequenced by the Edmann technique. The following sequence is obtained: LRPGSSLGLPAFSYSFFVIRNAK. This sequence has a 100% homology with human heparanase which is referenced in the IDQ9UL39 (Dempsey and al. 08/98) or IDQ9Y251 (Vlodavsky et al. 04/99) databases.
Exemple 2 : Exemples de formulations illustrant l'invention. Ces compositions ont été obtenues par simple mélange des différents composants.Example 2: Examples of formulations illustrating the invention. These compositions were obtained by simple mixing of the various components.
Composition 1 : Lotion antichute quotidienne :Composition 1: Daily fall protection lotion:
Heparanase 0,10 %Heparanase 0.10%
2,4 diaminopyrimidine-3-oxyde 0,75 %2,4 diaminopyrimidine-3-oxide 0.75%
Ethanol à 95° 30,00 %95% ethanol 30.00%
Parfum qs Colorants qsPerfume qs Colorants qs
Eau déminéralisée qsp 100,00 %Demineralized water qs 100.00%
Composition 2 : CRÈME DE SOIN :Composition 2: CARE CREAM:
Phase huileuse :Oily phase:
Cétéarylgiucoside (vendu sous la dénomination Montanov 68 par la société Seppic) 2,0 %Cetarylgiucoside (sold under the name Montanov 68 by the company Seppic) 2.0%
Alcool cétylique 1 ,5 %Cetyl alcohol 1.5%
Cire végétale (vendu sous la dénomination Suma Wax par la société Noda) 2,0 %Vegetable wax (sold under the name Suma Wax by the company Noda) 2.0%
Fraction liquide de beurre de karité 3,0 % Huile de noyau d'abricot 12,0 %Liquid fraction of shea butter 3.0% Apricot kernel oil 12.0%
Huile de noyau de mangues 2,0 %Mango kernel oil 2.0%
Diméthicone (vendue sous la dénomination Silicone L-45 par la société Union Carbide) 1 ,0 %Dimethicone (sold under the name Silicone L-45 by Union Carbide) 1.0%
Phase aqueuse :Aqueous phase :
Glycérine 3,0 %Glycerin 3.0%
Hydroxyéthylcellulose (gélifiant) 0,2 %Hydroxyethylcellulose (gelling agent) 0.2%
Sclerotium Gum (vendu sous la dénomination Amigel par la
société Alban Muller) (gélifiant) 0,5 0 //oSclerotium Gum (sold under the name Amigel by the Alban Muller company) (gelling agent) 0.5 0 // o
Amidon (charge) 0,4 %Starch (load) 0.4%
Heparanase 0,1 %0.1% Heparanase
Conservateurs qsPreservatives qs
Parfum 0,2 %0.2% fragrance
Eau qsp 100,0 %Water qs 100.0%
Le mode de préparation de l'emulsion consiste à mélanger la phase huileuse dans la phase aqueuse à une température d'environ 70°C à 80°C en agitant à la turbine.The mode of preparation of the emulsion consists in mixing the oily phase in the aqueous phase at a temperature of approximately 70 ° C to 80 ° C while stirring with a turbine.
Le produit obtenu est une emulsion huile-dans-eau qui a l'aspect d'une crème et peut être utilisée comme crème de nuit à appliquer quotidiennement.The product obtained is an oil-in-water emulsion which has the appearance of a cream and can be used as a night cream to be applied daily.
Composition 3 : Gel nettoyant à l'eauComposition 3: Cleansing gel with water
Butylène glycol 7,0 %Butylene glycol 7.0%
Saifcosinate de lauroyl sodium 4,0 %Lauroyl sodium saifcosinate 4.0%
Heparanase 0,1 %0.1% Heparanase
Triéthanolamine 0,8 % Carbomer 0,5 %Triethanolamine 0.8% Carbomer 0.5%
Conservateur qsConservative qs
Eau qsp 100,0 %Water qs 100.0%
Le gel obtenu possède de bonnes propriétés cosmétiques.
The gel obtained has good cosmetic properties.
Claims
1. Composition à usage cosmétique caractérisée par le fait qu'elle comprend au moins un polypeptide de la famille des héparanases.1. Composition for cosmetic use characterized in that it comprises at least one polypeptide from the heparanase family.
2. Composition selon la revendication 1 , caractérisée par le fait que le polypeptide est de l'héparanase humaine.2. Composition according to claim 1, characterized in that the polypeptide is human heparanase.
3. Composition selon l'une quelconque des revendications précédentes, caractérisée par le fait que le polypeptide est un précurseur de l'héparanase.3. Composition according to any one of the preceding claims, characterized in that the polypeptide is a precursor of heparanase.
4. Composition selon l'une quelconque des revendications 1 ou 2, caractérisée par le fait que le polypeptide est de l'héparanase fonctionnelle.4. Composition according to any one of claims 1 or 2, characterized in that the polypeptide is functional heparanase.
5. Composition selon l'une quelconque des revendications précédentes, caractérisée par le fait qu'elle contient un mélange de polypeptides issus de l'hydrolyse d'au moins un polypeptide de la famille des héparanases.5. Composition according to any one of the preceding claims, characterized in that it contains a mixture of polypeptides resulting from the hydrolysis of at least one polypeptide of the heparanase family.
6. Composition selon l'une quelconque des revendications précédentes, caractérisée par le fait que le polypeptide est un polypeptide d'origine naturelle.6. Composition according to any one of the preceding claims, characterized in that the polypeptide is a polypeptide of natural origin.
7. Composition selon l'une quelconque des revendications 1 à 5, caractérisée par le fait que le polypeptide est un polypeptide synthétique.7. Composition according to any one of claims 1 to 5, characterized in that the polypeptide is a synthetic polypeptide.
8. Composition selon l'une quelconque des revendications précédentes, caractérisée par le fait que le polypeptide est un polypeptide de fusion.8. Composition according to any one of the preceding claims, characterized in that the polypeptide is a fusion polypeptide.
9. Composition selon l'une quelconque des revendications précédentes, caractérisée par le fait que polypeptide de la famille des héparanases est en une quantité comprise entre 10"6% et 10% en poids total de la composition.9. Composition according to any one of the preceding claims, characterized in that the polypeptide of the heparanase family is in an amount between 10 "6 % and 10% by total weight of the composition.
10. Composition selon l'une quelconque des revendications précédentes,
caractérisée par le fait que polypeptide de la famille des héparanases est en une quantité comprise entre 0,1% et 1% en poids total de la composition.10. Composition according to any one of the preceding claims, characterized in that the polypeptide of the heparanase family is in an amount between 0.1% and 1% by total weight of the composition.
11. Utilisation dans une composition ou pour la préparation d'une composition, dans un milieu physiologiquement acceptable, d'au moins un polypeptide de la famille des héparanases, le polypeptide ou la composition étant destinés à favoriser la desquamation.11. Use in a composition or for the preparation of a composition, in a physiologically acceptable medium, of at least one polypeptide of the heparanase family, the polypeptide or the composition being intended to promote desquamation.
12. Utilisation dans une composition ou pour la préparation d'une composition, dans un milieu physiologiquement acceptable, d'au moins un polypeptide de la famille des héparanases, le polypeptide ou la composition étant destinés à moduler l'hydratation de la peau.12. Use in a composition or for the preparation of a composition, in a physiologically acceptable medium, of at least one polypeptide of the heparanase family, the polypeptide or the composition being intended to modulate the hydration of the skin.
13. Utilisation dans une composition ou pour la préparation d'une composition, dans un milieu physiologiquement acceptable, d'au moins un polypeptide de la famille des héparanases, le polypeptide ou la composition étant destinés à moduler la statut osmotique de la peau.13. Use in a composition or for the preparation of a composition, in a physiologically acceptable medium, of at least one polypeptide of the heparanase family, the polypeptide or the composition being intended to modulate the osmotic status of the skin.
14. Utilisation dans une composition ou pour la préparation d'une composition, dans un milieu physiologiquement acceptable, d'au moins un polypeptide de la famille des héparanases, le polypeptide ou la composition étant destinés à stimuler les défenses antimicrobienne de la peau.14. Use in a composition or for the preparation of a composition, in a physiologically acceptable medium, of at least one polypeptide of the heparanase family, the polypeptide or the composition being intended to stimulate the antimicrobial defenses of the skin.
15. Utilisation dans une composition ou pour la préparation d'une composition, dans un milieu physiologiquement acceptable, d'au moins un polypeptide de la famille des héparanases, le polypeptide ou la composition étant destinés à stimuler les défenses immunitaires de la peau.15. Use in a composition or for the preparation of a composition, in a physiologically acceptable medium, of at least one polypeptide of the heparanase family, the polypeptide or the composition being intended to stimulate the immune defenses of the skin.
16. Utilisation dans une composition ou pour la préparation d'une composition, dans un milieu physiologiquement acceptable, d'au moins un polypeptide de la famille des héparanases, le polypeptide ou la composition étant destinés moduler la différenciation cellulaire au niveau de la peau.
16. Use in a composition or for the preparation of a composition, in a physiologically acceptable medium, of at least one polypeptide of the heparanase family, the polypeptide or the composition being intended to modulate cellular differentiation in the skin.
17. Utilisation selon la revendication précédente, le polypeptide ou la composition étant destinés moduler la différenciation cellulaire au niveau de l'épiderme.17. Use according to the preceding claim, the polypeptide or the composition being intended to modulate cellular differentiation in the epidermis.
18. Utilisation dans une composition ou pour la préparation d'une composition, dans un milieu physiologiquement acceptable, d'au moins un polypeptide de la famille des héparanases, le polypeptide ou la composition étant destinés à moduler le renouvellement cellulaire au niveau de la peau.18. Use in a composition or for the preparation of a composition, in a physiologically acceptable medium, of at least one polypeptide of the heparanase family, the polypeptide or the composition being intended to modulate cell renewal in the skin .
19. Utilisation selon la revendication précédente, le polypeptide ou la composition étant destinés à moduler le renouvellement cellulaire au niveau de l'épiderme.19. Use according to the preceding claim, the polypeptide or the composition being intended to modulate cell renewal in the epidermis.
20. Utilisation dans une composition ou pour la préparation d'une composition, dans un milieu physiologiquement acceptable, d'au moins un polypeptide de la famille des héparanases, le polypeptide ou la composition étant destinés à moduler la prolifération des cellules de la peau.20. Use in a composition or for the preparation of a composition, in a physiologically acceptable medium, of at least one polypeptide of the heparanase family, the polypeptide or the composition being intended to modulate the proliferation of skin cells.
21. Utilisation selon la revendication précédente, le polypeptide ou la composition étant destinés à moduler la prolifération des cellules de l'épiderme.21. Use according to the preceding claim, the polypeptide or the composition being intended to modulate the proliferation of epidermal cells.
22. Utilisation dans une composition ou pour la préparation d'une composition, dans un milieu physiologiquement acceptable, d'au moins un polypeptide de la famille des héparanases, le polypeptide ou la composition étant destinés à moduler l'homéostasie des cellules de la peau.22. Use in a composition or for the preparation of a composition, in a physiologically acceptable medium, of at least one polypeptide of the heparanase family, the polypeptide or the composition being intended to modulate the homeostasis of skin cells .
23. Utilisation selon la revendication précédente, le polypeptide ou la composition étant destinés à moduler l'homéostasie des cellules de l'épiderme.23. Use according to the preceding claim, the polypeptide or the composition being intended to modulate the homeostasis of epidermal cells.
24. Utilisation dans une composition ou pour la préparation d'une composition, dans un milieu physiologiquement acceptable, d'au moins un
polypeptide de la famille des héparanases, le polypeptide ou la composition étant destinés à moduler la pousse des cheveux et/ou des poils.24. Use in a composition or for the preparation of a composition, in a physiologically acceptable medium, of at least one polypeptide of the heparanase family, the polypeptide or the composition being intended to modulate the growth of hair and/or body hair.
25. Utilisation selon l'une quelconque des revendications 11 à 24, le polypeptide étant tel que décrit dans l'une quelconque des revendications 1 à25. Use according to any one of claims 11 to 24, the polypeptide being as described in any one of claims 1 to
10.10.
26. Procédé de traitement cosmétique de la peau et/ou des cheveux, caractérisé par le fait que l'on applique sur celle-ci une composition telle que définie dans l'une quelconque des revendications 1 à 10.26. Process for cosmetic treatment of the skin and/or hair, characterized in that a composition as defined in any one of claims 1 to 10 is applied thereto.
27. Composition comprenant l'association d'au moins un polypeptide de la famille des héparanases et d'au moins un modulateur de l'expression dudit polypeptide.27. Composition comprising the combination of at least one polypeptide of the heparanase family and at least one modulator of the expression of said polypeptide.
28. Composition comprenant l'association d'au moins un polypeptide de la famille des héparanases et d'au moins un activateur de l'expression de l'héparanase.28. Composition comprising the combination of at least one polypeptide of the heparanase family and at least one activator of heparanase expression.
29. Composition comprenant l'association d'au moins un polypeptide de la famille des héparanases et d'au moins un inhibiteur de l'expression de l'héparanase.29. Composition comprising the combination of at least one polypeptide of the heparanase family and at least one inhibitor of heparanase expression.
30. Composition selon la revendication 29, caractérisée par le fait que le l'inhibiteur est choisi parmi l'héparane sulfate libre, les sucres libérés par l'action de l'héparanase, l'acide trachyspique, la suramine, les dérivés non anticoagulants de l'héparine
30. Composition according to claim 29, characterized in that the inhibitor is chosen from free heparan sulfate, sugars released by the action of heparanase, trachyspic acid, suramin, non-anticoagulant derivatives heparin
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR00/16320 | 2000-12-14 | ||
| FR0016320A FR2818131B1 (en) | 2000-12-14 | 2000-12-14 | COSMETIC COMPOSITION COMPRISING HEPARANASE |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| WO2002047654A2 true WO2002047654A2 (en) | 2002-06-20 |
| WO2002047654A3 WO2002047654A3 (en) | 2002-08-01 |
| WO2002047654A8 WO2002047654A8 (en) | 2003-05-15 |
Family
ID=8857661
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/FR2001/003936 WO2002047654A2 (en) | 2000-12-14 | 2001-12-11 | Cosmetic composition comprising heparanase |
Country Status (2)
| Country | Link |
|---|---|
| FR (1) | FR2818131B1 (en) |
| WO (1) | WO2002047654A2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004006949A1 (en) * | 2002-07-11 | 2004-01-22 | Hadasit Medical Research Services And Development Ltd. | Methods and compositions for regulation of mammalian hair growth |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1991002977A1 (en) * | 1989-08-23 | 1991-03-07 | Hadassah Medical Organization | Wound healing preparations containing heparanase |
| WO1999011798A1 (en) * | 1997-09-02 | 1999-03-11 | Insight Strategy & Marketing Ltd. | Polynucleotide encoding a polypeptide having heparanase activity and expression of same in transduced cells |
| WO1999040207A1 (en) * | 1998-02-09 | 1999-08-12 | Novartis Ag | HUMAN HEPARANASE POLYPEPTIDE AND cDNA |
| WO2001048161A2 (en) * | 1999-12-23 | 2001-07-05 | Schering Aktiengesellschaft | Human heparanase-related polypeptide and nucleic acid |
-
2000
- 2000-12-14 FR FR0016320A patent/FR2818131B1/en not_active Expired - Fee Related
-
2001
- 2001-12-11 WO PCT/FR2001/003936 patent/WO2002047654A2/en not_active Application Discontinuation
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1991002977A1 (en) * | 1989-08-23 | 1991-03-07 | Hadassah Medical Organization | Wound healing preparations containing heparanase |
| WO1999011798A1 (en) * | 1997-09-02 | 1999-03-11 | Insight Strategy & Marketing Ltd. | Polynucleotide encoding a polypeptide having heparanase activity and expression of same in transduced cells |
| WO1999040207A1 (en) * | 1998-02-09 | 1999-08-12 | Novartis Ag | HUMAN HEPARANASE POLYPEPTIDE AND cDNA |
| WO2001048161A2 (en) * | 1999-12-23 | 2001-07-05 | Schering Aktiengesellschaft | Human heparanase-related polypeptide and nucleic acid |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004006949A1 (en) * | 2002-07-11 | 2004-01-22 | Hadasit Medical Research Services And Development Ltd. | Methods and compositions for regulation of mammalian hair growth |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2002047654A3 (en) | 2002-08-01 |
| WO2002047654A8 (en) | 2003-05-15 |
| FR2818131A1 (en) | 2002-06-21 |
| FR2818131B1 (en) | 2005-02-11 |
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