EP3261613A1 - Particules d'acide hyaluronique pour des applications cosmétiques ou dermatologiques - Google Patents
Particules d'acide hyaluronique pour des applications cosmétiques ou dermatologiquesInfo
- Publication number
- EP3261613A1 EP3261613A1 EP16710260.7A EP16710260A EP3261613A1 EP 3261613 A1 EP3261613 A1 EP 3261613A1 EP 16710260 A EP16710260 A EP 16710260A EP 3261613 A1 EP3261613 A1 EP 3261613A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- carbon atoms
- hyaluronic acid
- particles
- group
- linear
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
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Classifications
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- 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
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
- A61K8/735—Mucopolysaccharides, e.g. hyaluronic acid; Derivatives thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
- A61K31/728—Hyaluronic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/0241—Containing particulates characterized by their shape and/or structure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- 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
- A61Q19/08—Anti-ageing preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/20—Chemical, physico-chemical or functional or structural properties of the composition as a whole
- A61K2800/30—Characterized by the absence of a particular group of ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/41—Particular ingredients further characterized by their size
- A61K2800/412—Microsized, i.e. having sizes between 0.1 and 100 microns
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/60—Particulates further characterized by their structure or composition
- A61K2800/65—Characterized by the composition of the particulate/core
- A61K2800/654—The particulate/core comprising macromolecular material
Definitions
- the present invention relates to the field of cosmetics or pharmaceutics, especially dermatological.
- the present invention relates to particles comprising hyaluronic acid modified with hydrophobic groups and their use as a stimulator of the epidermis and / or dermis.
- these assemblies are useful on the one hand as moisturizing and / or plumping agent and / or volumizer.
- these particles comprising hydrophobized hyaluronic acid are useful for reactivating the expression of endogenous hyaluronic acid thus making it possible to reduce and / or prevent skin imperfections such as the filling of wrinkles and fine lines.
- the particles of the invention are also useful for accelerating the healing of the skin or mucous membranes.
- Hyaluronic acid is a polysaccharide of the family of glycosaminoglycans consisting of two repeating units: ⁇ - (1,3) -gluronic acid and ⁇ - (1,4) -N-acetyl-D-glucosamine.
- This polysaccharide is widely present in the human body, especially among connective, epithelial and nervous tissues. More particularly, at the level of the skin, the production of hyaluronic acid makes it possible to fill the intercellular spaces and participates strongly in the hydration, the tonicity, the elasticity of the skin as well as the cohesion of the tissues.
- hyaluronic acid The decrease in the production of hyaluronic acid in the body from 40 years, is one of the explanations of skin aging. In recent years, this polymer has been widely used in the formulation of cosmetics to combat the effects of aging. High molecular weight hyaluronic acid (2,000 to 6,000 kDa) has very low activity in the epidermis and no activity in the dermis. Hyaluronic acid of high molar mass is not able to diffuse, and therefore to act, properly within the cutaneous structures. There is therefore a need to provide anti-aging formulations in which the diffusion of hyaluronic acid is facilitated both at the level of the epidermis and the dermis.
- the solution of the present invention is to provide hyaluronic acid in the form of particles. Unlike high molecular weight native hyaluronic acid which has very low activity, the particulate hyaluronic acid of the invention is capable of diffusing into the epidermis and into the dermis.
- the particulate formulation is made possible by using hydrophobized hyaluronic acid, i.e. modified hyaluronic acid by introducing hydrophobic groups.
- the hydrophobized hyaluronic acid particles of the invention are therefore of major interest for producing anti-aging formulations and obtaining a moisturizing and / or plumping and / or volumizing effect on the skin.
- the particles of the invention also have a healing effect of superficial wounds of the skin or mucous membranes.
- WO2013 / 15019 particles of inclusion complexes of hydrophobized hyaluronic acid and alpha-cyclodextrin as encapsulation systems.
- the particles of WO2013 / 150193 are intended to vectorize a substance of interest to a target tissue.
- WO2013 / 150193 does not indicate that its inclusion complex particles of hydrophobized hyaluronic acid and alpha-cyclodextrin could diffuse both in the epidermis and dermis and thus have an anti-aging effect.
- the present invention it has been found that by controlling the general hydrophobicity of hydrophobized hyaluronic acid, it is possible to obtain particles without the need to add cyclodextrin.
- the general hydrophobicity control of the hydrophobized hyaluronic acid can be done by playing on the following different aspects, whether simultaneously or not: the molar mass of the hyaluronic acid used;
- the general hydrophobicity of the hydrophobized hyaluronic acid used to form the particles of the invention can be evaluated by infrared spectroscopy.
- the intensity of the absorption bands characteristic of the alkyl functions is representative of the hydrophobicity.
- Intense bands are synonymous with too much hydrophobicity that makes it impossible to obtain particles, whereas less intense bands are characteristic of hydrophobized hyaluronic acid that can form particles alone.
- the invention therefore relates to the use in the cosmetic field of particles comprising hyaluronic acid modified with hydrophobic groups or its salts and / or derivatives, having formula (I):
- R 1 and R 2 each independently represent a hydrogen atom, an R group or a -COR group in which R represents:
- R 3 represents:
- X + represents a cation, preferably a sodium ion
- R 4 represents a hydrogen atom or a group R "chosen from:
- n represents the number of disaccharide units of DN-glucuronic acid and N-acetyl glucosamine and represents a strictly positive integer; with the proviso that at least one of R 1 or R 2 is -R or -COR; or R 3 represents a group -OR 'or a group -NHR'; or R 4 represents a group
- said particles not comprising a cyclodextrin.
- said particles are O-palmitoyl-hyaluronic acid, O-oleoyl-hyaluronic acid, O-stearyl-hyaluronic acid or O-lauryl-hyaluronic acid particles.
- the invention relates to the use of said particles as volumizing agent and / or plumping agent. According to one embodiment, the invention relates to the use of said particles to improve the hydration of the mucous membranes, the epidermis and the dermis.
- the invention relates to the use of said particles for limiting and / or correcting imperfections of the skin; preferably as a skin tightening agent or as an agent for the filling of wrinkles and / or fine lines of the skin.
- the invention also relates to particles comprising hyaluronic acid modified with hydrophobic groups, or its salts and / or derivatives, having formula (I):
- R 1 and R 2 each independently represent a hydrogen atom, an R group or a -COR group in which R represents:
- R 3 represents:
- X + represents a cation, preferably a sodium ion
- R 4 represents a hydrogen atom or a group R "chosen from:
- n represents the number of disaccharide units of DN-glucuronic acid and N-acetyl glucosamine and represents a strictly positive integer; with the proviso that at least one of R 1 or R 2 is -R or -COR; or R 3 represents a group -OR 'or a group -NHR'; or R 4 represents a group
- said particles not comprising a cyclodextrin; for their use as a medicine.
- the particles comprising hyaluronic acid for use as a medicament are used as a dermatological agent; preferably as a healing agent.
- the invention also relates to particles comprising hyaluronic acid modified with hydrophobic groups, or its salts and / or derivatives, having formula (I), as defined above.
- the particles of the invention comprise hyaluronic acid modified with hydrophobic groups, or its salts and / or derivatives, having formula (Ia):
- the invention also relates to a pharmaceutical composition
- a pharmaceutical composition comprising particles according to the invention and a pharmaceutically acceptable vehicle.
- the invention further relates to a medical device comprising particles according to the invention.
- the invention also relates to the use of a medical device according to the invention for repairing superficial lesions of the skin or mucous membranes; preferably to heal superficial wounds of the skin.
- Alkyl relates to a hydrocarbon chain, linear or branched, having from 1 to 1000 carbon atoms; preferably, from 1 to 60 carbon atoms, more preferably from 1 to 20 carbon atoms, more preferably, methyl, ethyl, propyl, isopropyl, w-butyl, sec-butyl, isobutyl, tert-butyl, pentyl, hexyl, heptyl octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, cetyl, heptadecyl, octadecyl, nonadecyl, eicosyl, oleoyl, linoleyl, linolenyl; still more preferably methyl, ethyl, propyl, isopropyl, n
- Alkene relates to an unsaturated hydrocarbon chain, linear or branched, comprising at least 2 carbon atoms, characterized by the presence of at least one covalent double bond between two carbon atoms;
- Cyclodextrin relates to a cyclic oligosaccharide composed of ⁇ -D-glucopyranose subunits linked by ⁇ - (1,4) linkages, such as, for example, alpha-cyclodextrin;
- Palmitoyl relates to a group -CO- (CH 2 ) 14-CH 3;
- Particles relates to assemblies comprising hyaluronic acid modified with hydrophobic groups.
- the term “particle” includes microparticles and / or nanoparticles obtained from hydrophobized hyaluronic acid;
- Hydrophilic relates to a compound or a chemical group having no affinity for water or aqueous media
- “Ride” or “Ridula” relates to a fold on the surface of the skin of a greater or lesser depth, caused by a loss of skin tone; in particular, by a rupture of the elastic fibers of the dermis with involvement of the connective tissue;
- “Hydration” refers to the action taken to achieve dryness of the skin; preferably, to fight against the drying of the epidermis and / or the dermis and / or mucous membranes, in particular to fight against the drying of the epidermis and / or dermis;
- Dermatis relates to the connective tissue forming the skin with the epidermis and the hypodermis.
- the dermis consists of the papillary dermis, the reticular dermis and the deep dermis;
- Papillary dermis relates to the connective tissue forming the skin composed of protruding papillae and juxtaposing the epidermis;
- Epidermis relates to the superficial layer of the skin whose surface is formed of keratinized dead cells;
- “Plumping agent” relates to a compound capable of causing a measurable increase in the density of the epidermis and / or dermis on any area of the human body.
- the "plumping" effect of the dermis or epidermis can be analyzed by the technique of fringe projection or ultrasound or by the implementation of techniques adapted to the area of the human body for which it is desired to highlight this effect ;
- Volumeizing agent relates to a compound capable of causing a measurable increase in the volume of the epidermis and / or the dermis on any area of the human body.
- the "volumizing" effect can be analyzed, measured and quantified by ultrasound or by the implementation of techniques adapted to the area of the human body for which it is desired to highlight this effect;
- “Tensing agent” relates to a compound capable of reducing the imperfections of the skin (preferably of the epidermis and / or the dermis) or of limiting their appearance; in particular, able to reduce wrinkles and / or fine lines in a subject;
- the "tensor" effect can be analyzed, measured and quantified by ultrasound or by the implementation of techniques adapted to the area of the human body for which it is desired to highlight this effect, for example using a cutometer.
- "Healing agent” relates to a compound capable of promoting the healing of wounds, in particular of superficial wounds, in particular superficial wounds of the skin or mucous membranes;
- Cosmetic use relates to a use intended to embellish and / or improve the appearance of the human body;
- Superficial wounds means a wound that only affects the skin layer or the immediately underlying tissues, such as but not limited to, a simple abrasion of the skin of small extent (abrasions or scratches);
- “Fatty acid” relates to a saturated or unsaturated carbon-containing aliphatic chain carboxylic acid having from 4 to 36 carbon atoms; preferably an acid carboxylic acid whose aliphatic carbon chain has from 4 to 28 atoms; more preferably, from 8 to 20 atoms;
- “Pharmaceutically acceptable” refers to the ingredients of a pharmaceutical composition that are compatible with each other and not deleterious to the patient.
- the subject of the invention is hyaluronic acid particles modified with hydrophobic groups, or its salts and / or derivatives.
- the invention relates to particles comprising hyaluronic acid modified with hydrophobic groups or its salts and / or derivatives, having formula (I):
- R 1 and R 2 each independently represent a hydrogen atom, an R group or a -COR group in which R represents:
- R 3 represents:
- X + represents a cation, preferably a sodium ion
- R 4 represents a hydrogen atom or a group R "chosen from:
- n represents the number of disaccharide units of DN-glucuronic acid and N-acetyl glucosamine and represents a strictly positive integer; with the proviso that at least one of R 1 or R 2 is -R or -COR; or R 3 represents a group -OR 'or a group -NHR'; or R 4 represents a group R ".
- the particles of the invention do not comprise cyclodextrin.
- the particles of the invention consist of hyaluronic acid modified with hydrophobic groups or its salts and / or derivatives, having formula (I).
- the hyaluronic acid is modified by acylation of the hydroxyl functions by fatty acids and their derivatives; preferably, fatty acids having a saturated or unsaturated carbonaceous aliphatic chain having from 4 to 36 carbon atoms; more preferably, a carbonaceous aliphatic chain having from 4 to 28 atoms; even more preferably, an aliphatic carbon chain having from 8 to 20 atoms.
- hyaluronic acid is modified with fatty acids and their derivatives; preferably, caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, arachidic acid, oleic acid, linoleic acid; this list is by no means exhaustive and limiting.
- the hyaluronic acid is modified with palmitic acid. According to one embodiment, the hyaluronic acid is modified with oleic acid. According to one embodiment, the hyaluronic acid is modified with lauric acid. According to one embodiment, the hyaluronic acid is modified with stearic acid.
- the preferred compounds of the invention are the compounds of formula (I) in which R 1 and R 2 each independently represent a hydrogen atom, a -R group or a -COR group in which R represents a linear alkyl group containing 15 or 16 carbon atoms.
- the modified hyaluronic acid is octyldodecyl erucate hyaluronate.
- the hyaluronic acid is not modified by an aromatic group.
- the particles of the invention comprise hyaluronic acid modified with hydrophobic groups or its salts and / or derivatives, having formula (Ia):
- R represents a linear alkyl group containing from 1 to 20 carbon atoms, preferably from 6 to 20 carbon atoms, more preferably from 7, 9, 11, 13, 15 , 17 or 19 carbon atoms.
- R represents a linear alkene group containing 6 to 20 carbon atoms, more preferably 7, 9, 11, 13, 15, 17 or 19 carbon atoms.
- R represents a linear alkene group comprising a C CC double bond.
- the hydrophobic groups are covalently attached to hyaluronic acid.
- the hydrophobic groups are covalently attached to hyaluronic acid by one or more oxygen atoms of said hyaluronic acid; especially at the level of the carboxylic function, and / or of a hydroxyl function of said hyaluronic acid.
- at least one of the hydroxyl groups of hyaluronic acid reacts with the fatty acids or their derivatives, such as but not limited to acid chlorides or acid anhydrides, to give covalent bonds ester type.
- the hydrophobic group is thus covalently bound to hyaluronic acid by one of its oxygen atoms, in the form of an acyl group (O-acylation reaction).
- the palmitic acid is covalently bound to hyaluronic acid by at least one of its oxygen atoms, in the form of an acyl group (O-acylation reaction).
- the acylation reaction is known to those skilled in the art. It is described for example in the international application published under the number WO2013 / 150193.
- the hydrophobic groups are covalently attached to hyaluronic acid by one or more oxygen atoms of said hyaluronic acid in proportions ranging from 0.001 to 100%; preferably, ranging from 0.1% to 70%; more preferably, from 0.5 to 20%; preferably from 0.5 to 20%.
- the hydrophobic groups are covalently attached to hyaluronic acid by one or more nitrogen atoms of said hyaluronic acid; especially at the amide or carboxylic function of said hyaluronic acid.
- the hydrophobic groups are covalently attached to hyaluronic acid by one or more nitrogen atoms of said hyaluronic acid in proportions ranging from 0.001 to 100%; preferably, ranging from 0.1% to 70%; more preferably, from 0.5 to 20%; preferably from 0.5 to 20%.
- the hydrophobic groups are covalently attached to hyaluronic acid by an ether bond.
- the hydrophobic groups are covalently attached to hyaluronic acid by an ester-type bond. According to one embodiment, the hydrophobic groups are covalently attached to hyaluronic acid by an amide bond. According to one embodiment, the hydrophobic groups are covalently attached to hyaluronic acid by a carbamate type bond.
- the degree of substitution of hyaluronic acid by the hydrophobic groups is in a range from 0.001% to 100%; preferably, ranging from 0.1% to 70%; more preferably, from 0.5 to 20%. According to one embodiment, the degree of substitution of hyaluronic acid by the hydrophobic groups is in a range from 0.01 to 20%, preferably from 0.2 to 10%, more preferably from 0.2 to 10%. 5%. According to a particular embodiment, the degree of substitution of hyaluronic acid by the hydrophobic groups is in a range from 0.2 to 1%, preferably from 0.2 to 0.5%.
- the degree of substitution of hyaluronic acid by the hydrophobic groups is in a range from 20 to 60%, preferably from 25 to 55%, more preferably from 30 to 50%.
- the degree of substitution reflects the number of hydrophobic groups bound to 100 saccharide units of the hyaluronic acid chain. It is determined by the experimental conditions of the grafting and can be measured by nuclear magnetic resonance (NMR) or by elemental analysis for example. This parameter has an influence on the particle size.
- the hyaluronic acid modified with hydrophobic groups is composed of at least 3 disaccharide units, Le. n is at least 3, its molar mass being in particular in a range from 100 Da to 1 000 000 kDa; preferably, its molar mass is in a range from 100 Da to 3,000,000 Da; preferably from 5k Da to 5000kDa; more preferably, is 7.5 kDa, 51 kDa or 2,000 kDa.
- the hydrophobized hyaluronic acid is of low molar mass, Le. having a molar mass of less than or equal to 15 kDa.
- the hydrophobized hyaluronic acid is of average molar mass, Le. having a molar mass ranging from 15 kDa to 100 kDa.
- the hydrophobized hyaluronic acid is of high molar mass, Le. having a molar mass greater than 100 kDa, more preferably greater than 1000 kDa.
- the hydrophobized hyaluronic acid has a molar mass ranging from 100 kDa to 1000 kDa, preferably from 100 kDa to 500 kDa.
- the hydrophobized hyaluronic acid has a molar mass ranging from 1000 kDa to 5000 kDa, preferably from 2000 kDa to 4000 kDa.
- the particles of the invention comprise hydrophobized hyaluronic acid of formula (I) having:
- a high molar mass ranging from 1000 kDa to 5000 kDa, preferably from 2000 kDa to 4000 kDa;
- a degree of substitution ranging from 0.01 to 20%, preferably from 0.2 to 5%, more preferably from 0.2 to 1%, even more preferably from 0.2 to 0.5%.
- the particles of the invention comprise hydrophobized hyaluronic acid of formula (I) having:
- an average molar mass ranging from 15 kDa to 1000 kDa, preferably from
- the particles of the invention comprise hydrophobized hyaluronic acid of formula (I) having:
- a low molar mass less than 15 kDa, preferably ranging from 1 to 10 kDa, more preferably ranging from 5 to 10 kDa; and a degree of substitution ranging from 0.01 to 20%, preferably from 0.1 to 5%, more preferably from 0.2 to 1.5%, even more preferably from 0.2 to 1.0%.
- the particles of the invention comprise hydrophobized hyaluronic acid of formula (I) of controlled hydrophobicity.
- the hydrophobicity of the hydrophobized hyaluronic acid of the invention can be evaluated by infrared spectroscopy.
- the intensity of the infrared absorption bands characteristic of the alkyl functions is representative of the hydrophobicity.
- Intense absorption bands are synonymous with high hydrophobicity that makes it impossible to obtain particles, whereas less intense bands are characteristic of hydrophobized hyaluronic acid that can form particles alone.
- the particles of the invention comprise hydrophobized hyaluronic acid of formula (I) having infrared spectroscopy absorption bands characteristic of alkyl functions having a low or medium intensity.
- the infrared spectroscopic absorption bands characteristic of the alkyl functions have wavenumbers of the order of 2800-3000 cm -1 .
- the infrared spectroscopic absorption bands characteristic of the hydroxyl functions have wave numbers of order 3200-3700 cm "1 .
- Infrared spectra can be recorded on conventional devices known to those skilled in the art. In particular, a Fourier transform infrared spectrometer can be used.
- the particles of the invention comprise hyaluronic acid modified with hydrophobic groups or its salts and / or derivatives, having formula (Ia):
- n represents the number of disaccharide units of ⁇ - ⁇ -glucuronic acid and N-acetyl glucosamine and represents a strictly positive integer
- R 1 and R 2 each independently represent a hydrogen atom, an R group or a -COR group in which R represents:
- a linear or branched alkyl group preferably linear, having 1 to 20 carbon atoms, preferably 6 to 20 carbon atoms, more preferably from 7, 9, 11, 13, 15, 17 or 19 carbon atoms ; or
- a high molar mass ranging from 1000 kDa to 5000 kDa, preferably from 2000 kDa to 4000 kDa;
- a degree of substitution ranging from 0.01 to 20%, preferably from 0.2 to 5%, more preferably from 0.2 to 1%, even more preferably from 0.2 to 0.5%.
- the particles of the invention comprise hyaluronic acid modified with hydrophobic groups or its salts and / or derivatives, having formula (Ia):
- n represents the number of disaccharide units of ⁇ - ⁇ -glucuronic acid and N-acetyl glucosamine and represents a strictly positive integer
- R 1 and R 2 each independently represent a hydrogen atom, an R group or a -COR group in which R represents:
- a linear or branched alkyl group preferably linear, having 1 to 20 carbon atoms, preferably 6 to 20 carbon atoms, more preferably from 7, 9, 11, 13, 15, 17 or 19 carbon atoms ; or
- an average molar mass ranging from 15 kDa to 1000 kDa, preferably from 30 kDa to 70 kDa;
- a degree of substitution ranging from 0.01 to 20%, preferably from 0.1 to 5%, more preferably from 0.15 to 1.5%, even more preferably from 0.15 to 1.0%.
- the particles of the invention comprise hyaluronic acid modified with hydrophobic groups or its salts and / or derivatives, having formula (Ia):
- n represents the number of disaccharide units of ⁇ - ⁇ -glucuronic acid and N-acetyl glucosamine and represents a strictly positive integer
- R 1 and R 2 each independently represent a hydrogen atom, an R group or a -COR group in which R represents:
- a linear or branched alkyl group preferably linear, having 1 to 20 carbon atoms, preferably 6 to 20 carbon atoms, more preferably from 7, 9, 11, 13, 15, 17 or 19 carbon atoms ; or
- a low molar mass less than 15 kDa, preferably from 1 to
- a degree of substitution ranging from 0.01 to 20%, preferably from 0.1 to 5%, more preferably from 0.2 to 1.5%, even more preferentially from 0.2 to
- the particles of the invention are microparticles or nanoparticles comprising hyaluronic acid modified with hydrophobic groups of formula (I). According to one embodiment, the particles of the invention are microparticles or nanoparticles consisting of hyaluronic acid modified with hydrophobic groups of formula (I).
- the particles comprising hydrophobized hyaluronic acid have a size ranging from 1 nm to 100,000 nm; preferably from 10 nm to 1000 nm; preferably from 1000 nm to 100,000 nm; more preferably less than 500 nm.
- the particles consist of at least two polysaccharides modified with hydrophobic groups of formula (I). According to one embodiment, the particles consist of a mixture of at least two polysaccharides chosen from hyaluronic acids modified with hydrophobic groups of formula (D-
- the particles are O-palmitoyl-hyaluronic acid particles. particles comprising hyaluronic acid modified with palmitic acid by an O-acylation reaction.
- the particles are particles of O-oleoyl-hyaluronic acid, Le. particles comprising hyaluronic acid modified with oleic acid by an O-acylation reaction.
- the particles are O-stearyl hyaluronic acid particles. particles comprising hyaluronic acid modified with stearic acid by an O-acylation reaction.
- the particles are O-lauryl-hyaluronic acid particles. particles comprising hyaluronic acid modified with lauric acid by an O-acylation reaction. According to one embodiment, the particles are particles of O-palmitoyl-hyaluronic acid, O-oleoyl-hyaluronic acid, O-stearyl hyaluronic acid or O-lauryl-hyaluronic acid. According to one embodiment, the particles comprising hydrophobized hyaluronic acid further comprise a cosmetic agent; especially a depigmenting agent, healing, moisturizing, perfuming, deodorant, antiperspirant, cleanser, dye, preservative, volumizer and / or plumping, tensor. Process for preparing the particles
- the present invention also relates to a process for preparing particles of hydrophobized hyaluronic acid.
- the process for preparing hydrophobized hyaluronic acid particles comprises a step of mixing at least: two hydrophobized hyaluronic acids having formula (I):
- the method for forming the particles of the invention comprises the hydrophobized hyaluronic acid dispersion of formula (I) according to the invention, in an aqueous dispersion medium.
- the aqueous dispersion medium for forming the particles is selected from: water, a buffer or a mixture thereof.
- the buffer may be a phosphate buffer.
- the process for preparing the particles is carried out with stirring, in particular magnetic stirring, at a stirring speed of from 50 to 1000 rpm; preferably at a stirring speed of from 100 to 500 revolutions / minute; more preferably, at a stirring speed of about 200 rpm.
- the process for preparing the particles is carried out at a temperature of from 4 to 100 ° C .; preferably at a temperature of 10 to 35 ° C; more preferably, at a temperature of about 20 ° C. According to a particularly preferred embodiment, the process for preparing the particles of the invention is carried out at room temperature.
- the process for preparing the particles is carried out at a duration of the stirring being in a range from 2 hours to 15 days; preferably, this time is in a range from 24 hours to 48 hours; more preferably, is approximately equal to 36 hours.
- the hydrophobized hyaluronic acid of formula (I) according to the invention is at a final concentration in the aqueous dispersion medium of 0.1 to 5% by weight, preferably of 0.25 to 2% by weight.
- the present invention also relates to hydrophobized hyaluronic acid particles obtained by the above particle preparation method.
- the present invention also relates to a process for the preparation of hydrophobized hyaluronic acid of formula (I) according to the invention, in which at least one of R 1 or R 2 represents a group-COR.
- the method of the invention comprises an O-acylation step between hyaluronic acid and a fatty acid or a fatty acid derivative.
- the O-acylation step is carried out at room temperature. Control of the O-acylation temperature advantageously makes it possible to modulate the degree of final substitution of the hydrophobized hyaluronic acid of the invention and thus to control its hydrophobicity.
- the O-acylation step is carried out with stirring, in particular magnetic stirring, at a stirring speed of from 50 to 1000 rpm; preferably, at a stirring speed of from 100 to 500 rpm; more preferably, at a stirring speed of about 250 rpm.
- the O-acylation step is carried out for a duration ranging from 2 hours to 5 days; preferably, this time is in a range from 48 hours to 72 hours; more preferably, is about 72 hours.
- compositions comprising hydrophobized hyaluronic acid particles of formula (I) as defined above, in association with a pharmaceutically or cosmetically acceptable excipient.
- the particles entering into the compositions of the invention are particles which are completely or essentially composed of hydrophobized hyaluronic acid of formula (I) as defined above.
- the particles entering the compositions of the invention do not comprise cyclodextrin.
- the compositions of the invention comprise an amount of said particles in a range from 10 ⁇ 10 % to 100% by weight relative to the total mass of the composition, preferably from 0.0001% to 50%, very preferably of 0.001% and 10% by weight relative to the total mass of the composition.
- the composition is in solid form, or in the form of a solution, suspension or emulsions such as water-in-oil (W / O), oil-in-water (O / W) or water-in-oil emulsions. in water (W / O / W), in which the oil is of vegetable or mineral nature, in a biocompatible medium.
- the composition further comprises a solvent; preferably biocompatible.
- the composition further comprises a solvent selected from aqueous or hydro-alcoholic solutions.
- the composition further comprises at least one cosmetically acceptable excipient, usable in the form of gels, pastes, ointments, lotions, creams, milks, sticks, shampoos, powders, aerosols, patches.
- compositions used in the cosmetic treatment process of the human body also comprise many types of adjuvants or active ingredients chosen from at least one of the following ingredients: fatty substances, organic solvents, thickeners , gelling agents, softeners, detergent surfactants, superfatting agents, thickening and / or gelling surfactants, antioxidants, opacifiers, stabilizers, foaming agents, fragrances, emulsifying surfactants, hydrotropic agents, plasticizing agents, superfatting agents, texturizing agents, pigments, sequestering agents, chelators, preservatives, chemical filters or mineral filters, essential oils, dyestuffs, pigments hydrophilic or lipophilic active agents, humectants, for example glycerol, preservatives, dyes, perfumes, cosmetic active agents, mineral or organic sunscreens, organic mineral arches such as iron oxides, titanium oxides and talc, synthetic fillers such as nylons and poly (methacrylate) crosslinked or not, silicone elastomers,
- compositions comprising hydrophobized hyaluronic acid of formula (I) are administered by direct topical route.
- compositions comprising hydrophobized hyaluronic acid of formula (I) are administered by indirect topical route.
- indirect topical route means the use of a textile support or nonwoven materials to administer the composition.
- the invention relates to the use of particles comprising hyaluronic acid modified with hydrophobic groups, or its salts and / or derivatives.
- particles comprising hyaluronic acid modified with hydrophobic groups or its salts and / or derivatives having formula (I):
- R 1 and R 2 each independently represent a hydrogen atom, an R group or a -COR group in which R represents:
- a linear or branched alkene group containing 2 to 1000 carbon atoms and bearing at least one C C double bond;
- R 3 represents:
- X + represents a cation, preferably a sodium ion
- R 4 represents a hydrogen atom or a group R "chosen from:
- n represents the number of disaccharide units of DN-glucuronic acid and N-acetyl glucosamine and represents a strictly positive integer; with the proviso that at least one of R 1 or R 2 is -R or -COR; or R 3 represents a group -OR 'or a group -NHR'; or R 4 represents a group R ".
- the present invention also relates to the use of particles consisting completely or essentially of hyaluronic acid modified with hydrophobic groups of formula (I); preferably, linear or branched, especially linear, alkyl or alkenyl groups containing from 1 to 60 carbon atoms; more preferably, containing from 1 to 20 carbon atoms.
- hydrophobic groups of formula (I) preferably, linear or branched, especially linear, alkyl or alkenyl groups containing from 1 to 60 carbon atoms; more preferably, containing from 1 to 20 carbon atoms.
- the present invention relates to the use of hyaluronic acid modified with hydrophobic groups; preferably, linear or branched, especially linear, alkyl or alkenyl groups containing from 1 to 60 carbon atoms; more preferably, containing from 1 to 20 carbon atoms.
- the present invention relates to the use of particles comprising hydrophobized hyaluronic acid, or its salts and / or derivatives, obtained by a preparation process comprising a step of mixing at least: two hydrophobized hyaluronic acids having the formula (I):
- the subject of the invention is also the use of particles comprising hyaluronic acid modified with hydrophobic groups, or of its salts and / or derivatives, in the cosmetic field and / or in the pharmaceutical, especially dermatological, field.
- the particles used in the cosmetic field and / or the pharmaceutical field are particles consisting of hyaluronic acid.
- the particles used in the cosmetics field and / or the pharmaceutical field are particles not comprising a cyclodextrin.
- the invention relates to the use in the cosmetic field of hyaluronic acid particles modified with hydrophobic groups, or its salts and / or derivatives, having the formula (I):
- R 1 and R 2 each independently represent a hydrogen atom, an R group or a -COR group in which R represents:
- R 3 represents:
- X + denotes a cation, preferably a sodium ion
- R 4 represents a hydrogen atom or a group R "chosen from:
- n represents the number of disaccharide units of DN-glucuronic acid and N-acetyl glucosamine and represents a strictly positive integer; with the proviso that at least one of R 1 or R 2 is -R or -COR; or R 3 represents a group -OR 'or a group -NHR'; or R 4 represents a group R ".
- the invention relates to the cosmetic use of particles comprising hyaluronic acid modified with hydrophobic groups of formula (I) as a cosmetic agent; preferably, as volumizing agent and / or plumping agent.
- a cosmetic agent preferably, as volumizing agent and / or plumping agent.
- the O-palmitoyl-hyaluronic acid, O-oleoyl-hyaluronic acid, O-stearyl-hyaluronic acid or O-lauryl-hyaluronic acid particles are useful as cosmetic agents; preferably, as volumizing agent and / or plumping agent.
- the O-palmitoyl-hyaluronic acid particles are useful as a cosmetic agent; preferably, as volumizing agent and / or plumping agent.
- the Applicant has demonstrated the action of the particles of the invention for its action in the epidermis and the dermis.
- the Applicant has demonstrated the action of the particles of the invention as a stimulating agent for the production of endogenous hyaluronic acid.
- the particles of the invention thus advantageously make it possible to fight against the thinning of the skin.
- the subject of the invention is the cosmetic use of hydrophobized hyaluronic acid particles of formula (I), characterized in that the particles of hydrophobized hyaluronic acid of formula (I) further promote the expansion connective tissues of human skin; preferably, the epidermis and the dermis.
- expansion of the connective tissues of human skin means any increase in the mass and / or volume and / or thickness of the connective tissues of human skin; preferably, the epidermis and the dermis.
- the O-palmitoyl-hyaluronic acid, O-oleoyl-hyaluronic acid, O-stearyl-hyaluronic acid or O-lauryl-hyaluronic acid particles promote the expansion of the connective tissues. human skin; preferably, the epidermis and the dermis. According to one embodiment, the O-palmitoyl-hyaluronic acid particles promote the expansion of the connective tissues of human skin; preferably, the epidermis and the dermis.
- the subject of the invention is the cosmetic use of hydrophobized hyaluronic acid particles for limiting and / or correcting imperfections of the skin; preferably as a skin tightening agent or as an agent for the filling of wrinkles and / or fine lines of the skin.
- the O-palmitoyl-hyaluronic acid, O-oleoyl-hyaluronic acid, O-stearyl-hyaluronic acid or O-lauryl-hyaluronic acid particles are useful for limiting and / or correct skin imperfections; preferably as a skin tightening agent or as an agent for the filling of wrinkles and / or fine lines of the skin.
- O-palmitoyl-hyaluronic acid particles are useful for limiting and / or correcting skin imperfections; preferably as a skin tightening agent or as an agent for the filling of wrinkles and / or fine lines of the skin.
- the subject of the invention is the cosmetic use of hydrophobized hyaluronic acid particles of formula (I), characterized in that the hydrophobized hyaluronic acid particles of formula (I) also stimulate an increase of the elasticity of the skin.
- the O-palmitoyl-hyaluronic acid, O-oleoyl-hyaluronic acid, O-stearyl-hyaluronic acid or O-lauryl-hyaluronic acid particles are useful for increasing the elasticity. of the skin. According to one embodiment, the O-palmitoyl-hyaluronic acid particles are useful for increasing the elasticity of the skin.
- the subject of the invention is the cosmetic use of hydrophobized hyaluronic acid particles to improve the hydration of the mucous membranes, the epidermis and the dermis, in particular to improve the hydration of the epidermis. and dermis.
- the hydrophobized hyaluronic acid particles are useful for combating the drying of the mucous membranes.
- the hydrophobized hyaluronic acid particles are useful for combating drying of the skin; preferably, the epidermis and the dermis.
- O-palmitoyl-hyaluronic acid, O-oleoyl-hyaluronic acid, O-stearyl-hyaluronic acid or O-lauryl-hyaluronic acid particles are useful for improving hydration. epidermis and dermis. According to one embodiment, the O-palmitoyl-hyaluronic acid particles are useful for improving the hydration of the epidermis and dermis. According to one embodiment, O-palmitoyl-hyaluronic acid, O-oleoyl-hyaluronic acid, O-stearyl-hyaluronic acid or O-lauryl-hyaluronic acid particles are useful for combating desiccation.
- the skin preferably, the epidermis and the dermis.
- the O-palmitoyl-hyaluronic acid particles are useful for combating the drying of the skin; preferably, the epidermis and the dermis.
- the uses of the particles of the present invention are intended for mature and / or aged skin.
- the subject of the invention is the cosmetic use of particles comprising hydrophobized hyaluronic acid as encapsulants for cosmetically active ingredients.
- the subject of the invention is the cosmetic use of particles comprising hydrophobized hyaluronic acid as inclusion complexes of cosmetically active ingredients.
- the hydrophobized hyaluronic acid particles are not used as encapsulating agents.
- the hydrophobized hyaluronic acid particles are not used as inclusion complexes.
- the invention relates to a cosmetic treatment method of the human body.
- the invention relates to the use of particles comprising hydrophobized hyaluronic acid, or its salts and / or derivatives, as a cosmetic agent.
- the invention relates to particles comprising hyaluronic acid modified with hydrophobic groups or its salts and / or derivatives, for their use in the pharmaceutical field, as a medicament, having the formula (I):
- R 1 and R 2 each independently represent a hydrogen atom, an R group or a -COR group in which R represents:
- R 3 represents:
- X + represents a cation, preferably a sodium ion
- R 4 represents a hydrogen atom or a group R "chosen from:
- n represents the number of disaccharide units of DN-glucuronic acid and N-acetyl glucosamine and represents a strictly positive integer; with the proviso that at least one of R 1 or R 2 is -R or -COR; or R 3 represents a group -OR 'or a group -NHR'; or R 4 represents a group R ".
- the subject of the invention is hyaluronic acid particles modified with hydrophobic groups of formula (I) for their use as a dermatological agent.
- the subject of the invention is hyaluronic acid particles modified with hydrophobic groups of formula (I) for their use as a dermatological agent; preferably as a healing agent; more preferably as a healing agent for superficial wounds, especially skin or mucous membranes.
- the O-palmitoyl-hyaluronic acid, O-oleoyl-hyaluronic acid, O-stearyl-hyaluronic acid or O-lauryl-hyaluronic acid particles are useful as dermatological agents; preferably as a healing agent for superficial wounds.
- the O-palmitoyl-hyaluronic acid particles are useful as a dermatological agent; preferably as a healing agent for superficial wounds.
- the subject of the invention is particles comprising hydrophobized hyaluronic acid for use as a dermatological agent; preferably, to limit and / or correct skin imperfections.
- the O-palmitoyl-hyaluronic acid, O-oleoyl-hyaluronic acid, O-stearyl-hyaluronic acid or O-lauryl-hyaluronic acid particles are useful as dermatological agents; preferably, to limit and / or correct skin imperfections.
- the O-palmitoyl-hyaluronic acid particles are useful as dermatological agents; preferably, to limit and / or correct skin imperfections.
- the subject of the invention is hydrophobized hyaluronic acid particles of formula (I) for their use as a dermatological agent, characterized in that the hydrophobized hyaluronic acid particles of formula (I) stimulate, moreover, an increase in the elasticity of the skin.
- the O-palmitoyl-hyaluronic acid, O-oleoyl-hyaluronic acid, O-stearyl-hyaluronic acid or O-lauryl-hyaluronic acid particles are useful for increasing the elasticity. skin.
- the O-palmitoyl-hyaluronic acid particles are useful for increasing the elasticity of the skin.
- the subject of the invention is hydrophobized hyaluronic acid particles for use as a dermatological agent, characterized in that the hydrophobized hyaluronic acid particles of formula (I) improve the hydration mucous membranes, epidermis and dermis, especially the epidermis and dermis.
- the hydrophobized hyaluronic acid particles are useful for combating the drying of the mucous membranes.
- the hydrophobized hyaluronic acid particles are useful for combating drying of the skin; preferably, the epidermis and the dermis.
- the O-palmitoyl-hyaluronic acid, O-oleoyl-hyaluronic acid, O-stearyl hyaluronic acid or O-lauryl-hyaluronic acid particles are useful for improving the hydration of the epidermis and dermis.
- the O-palmitoyl-hyaluronic acid particles are useful for improving the hydration of the epidermis and dermis.
- O-palmitoyl-hyaluronic acid, O-oleoyl-hyaluronic acid, O-stearyl-hyaluronic acid or O-lauryl-hyaluronic acid particles are useful for combating desiccation. skin ; preferably, the epidermis and the dermis.
- the O-palmitoyl-hyaluronic acid particles are useful for combating the drying of the skin; preferably, the epidermis and the dermis.
- the subject of the invention is particles of hydrophobized hyaluronic acid for use as a dermatological agent; preferably as encapsulating agents.
- the subject of the invention is particles of hydrophobized hyaluronic acid for use as a dermatological agent; preferably, as inclusion complexes.
- the hydrophobized hyaluronic acid particles are not used as encapsulating agents for dermatologically active ingredients. According to one embodiment, the hydrophobized hyaluronic acid particles are not used as inclusion complexes of dermatologically active ingredients. According to one embodiment, the invention relates to particles comprising hyaluronic acid modified with hydrophobic groups, or its salts and / or derivatives, in the preparation of compositions for the dermatological treatment of an individual; preferably for the treatment of the epidermis and / or dermis.
- FIG. 1 represents the characteristic IR spectrum of the native hyaluronic acid (FIG. 1A) and the hyaluronic acid modified with hydrophobic groups according to example 1.1.1 (FIG. 1B), 1.2 (FIG. 1C), 1.3 (FIG. 1D). ), or 1.4 (Figure 1E).
- Figure 2 is a graph showing the intensity of penetration into the epidermis (EP) and the papillary dermis (DP) of hydrophobized hyaluronic acid for the formulation Al tested in Example 3.1.
- HABP Biotinylated Hyaluronic Acid Protein
- the spectra were recorded as a function of time under a stream of dinitrogen using an FT / IR-4100 JASCO infrared spectrometer.
- the principle is to put in contact between a crystal (diamond) and the sample to be analyzed before being crossed by an infrared beam.
- the particle sizes were evaluated by the hydrodynamic diameter. Measurements of the average hydrodynamic diameters of the nanoparticles and microparticles were carried out with a Nano-ZS90 nanoseries Zetasizer from Malvern Instruments SA (Orsay, France) by quasi-elastic light scattering.
- IR spectroscopy analysis is a fast and efficient method for identifying chemical groups of hydrophobized hyaluronic acid (FIG. 1B) compared to the spectrum of native hyaluronic acid (FIG. 1A).
- Example 1.1.1 The product was characterized by elemental analysis and degree of calcium substitution as in Example 1.1.1:
- the O-palmitoyl-hyaluronic acid AH-4-AP obtained according to Example 1.1.1 is dispersed in water.
- the medium is mixed for 72 hours at room temperature to form the particles.
- Particles were formed by dispersing 2000 kDa hydrophobized hyaluronic acid chains, as described in Examples 1.1.1, 1.2, 1.3 and 1.4, in water.
- the experimental conditions are specified in Table 2. A dilution by 2 was performed then the medium was stirred for 72h at room temperature.
- Hyaluronic acid Quantity of acid Quantity of water in the hydrophobized hyaluronic mixture (g)
- Particles were formed by dispersing 51 kDa or 7.5 kDa hyaluronic acid O-palmitoyl chains as described in Examples 1.1.2 and 1.1.3 in water at a concentration of 1%. mass.
- Hydration and the attenuation of the effects of aging of the skin require the availability of formulations comprising active compounds capable of effectively penetrating the epidermis (EP) then the papillary dermis (PD) of an individual.
- Formulation A1 particles comprising O-palmitoyl-hyaluronic acid AH-4-AP (molar mass of about 2 MDa) obtained according to the protocol of Example 2, Formulation A1 was stored at room temperature before and during the duration of the study.
- Table 3 shows the various batches tested.
- hyaluronic acid was performed on paraffin Formol sections with a biotinylated hyaluronic acid anti-acid (HABP) (Seikagaku, ref 400763-1 A), at 1 / 100th for 1 hour at room temperature with a biotin amplifying system. / streptavidin, revealed by Vector ® VJP commercial developer (SK 4600).
- the labeling was performed using an immunostaining automaton (Dako, AutostainerPlus).
- the labeling was then evaluated by microscopic examination and quantified in image analysis using the CellD software.
- control batches on day 0 and day 10 show a weak labeling of hyaluronic acid in the epidermis and a mean marking in the papillary dermis;
- the treatment of the explants with the formulation Al comprising hydrophobized hyaluronic acid AH-4-AP has a clear marking of the hyaluronic acid both in the epidermis and the papillary dermis.
- Formulation A2 particles comprising O-stearyl hyaluronic acid (AH-4-AS) obtained according to the protocol of Example 2,
- Formulation A3 Particles comprising O-oleoyl-hyaluronic acid (AH-4-AO) obtained according to the protocol of Example 2. The products were stored at ambient temperature before and during the duration of the study.
- AH-4-AO O-oleoyl-hyaluronic acid
- hyaluronic acid was performed on paraffin Formol sections with a biotinylated hyaluronic acid anti-acid (HABP) (Seikagaku, ref 400763-1 A), at 1 / 100th for 1 hour at room temperature with a biotin amplifying system. / streptavidin, revealed by Vector ® VJP commercial developer (SK 4600).
- the labeling was performed using an immunostaining automaton (Dako, AutostainerPlus).
- the labeling was then evaluated by microscopic examination and quantified in image analysis using the CellD software.
- the results showed for the A2 and A3 formulations, an overall morphology improved compared to the control group after nine days.
- the epidermal layer is thicker and the relief of the dermal-epidermal junction is improved.
- the labeling results show that the application of the A2 and A3 formulations topically induces an increase in the expression of hyaluronic acid in both the epidermis and the dermis.
- hydrophobized hyaluronic acid particles of the invention exhibit anti-aging activity.
- EXAMPLE 4 Study by Image Analysis of the Density and / or Thickness Variation of the Epidermis and / or the Papillary Dermis in the Presence of Hydrophobized Hyaluronic Acid Particles
- Sections of 5 ⁇ were made according to the MO-H-173 procedure using a Minot microtome, Leica RM 2125 and mounted on Superfrost® histological glass slides.
- the particles of the invention can stimulate the production of endogenous hyaluronic acid both in the epidermis and in the dermis.
- the aim is to evaluate the action of O-palmitoyl-hyaluronic acid particles AH-4-AP on the healing of superficial burns from ex-vivo skin explants.
- Example 2 the O-palmitoyl-hyaluronic acid particles obtained according to the protocol of Example 2 (formulation A4); and a commercial product (Cicalfate, AVENE) known as a restorative cream for superficial wounds of the skin.
- AVENE commercial product
- each explant was placed in HBSS (Hank's Balanced Saline Solution) medium and irradiated at the center with a dose of 10J / cm 2 of ultraviolet B light using a Vilbert Lourmat RMX 3W solar stimulator. topically applied at 2 mg / cm 2 of product (spread with a small spatula) on the explants on days D0 (after irradiation), D2, D3, D6 and D8, the explants of lots T and B did not received no treatment except the renewal of the medium.
- the samples were dehydrated and impregnated in paraffin using a Leica TP 1020 dehydration automaton. was packaged using a Leica EG 1160 coating station. 5 ⁇ sections were made using a Minot microtome, Leica RM 2125 and mounted on Superfrost histological glass slides. ®.
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Abstract
Description
Claims
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Application Number | Priority Date | Filing Date | Title |
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FR1551711A FR3033134B1 (fr) | 2015-02-27 | 2015-02-27 | Particules d'acide hyaluronique pour des applications cosmetiques ou dermatologiques |
PCT/FR2016/050447 WO2016135430A1 (fr) | 2015-02-27 | 2016-02-26 | Particules d'acide hyaluronique pour des applications cosmétiques ou dermatologiques |
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EP3261613A1 true EP3261613A1 (fr) | 2018-01-03 |
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EP16710260.7A Withdrawn EP3261613A1 (fr) | 2015-02-27 | 2016-02-26 | Particules d'acide hyaluronique pour des applications cosmétiques ou dermatologiques |
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US (1) | US20180036220A1 (fr) |
EP (1) | EP3261613A1 (fr) |
FR (1) | FR3033134B1 (fr) |
WO (1) | WO2016135430A1 (fr) |
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WO2018024902A1 (fr) * | 2016-08-04 | 2018-02-08 | Biokawthar Technologies | Utilisations d'acide hyaluronique modifié de manière hydrophobe par des liaisons amide et/ou hydrazide en cosmétique et/ou en dermatologie |
US11939408B2 (en) * | 2019-12-20 | 2024-03-26 | Massachusetts Institute Of Technology | Hyaluronic acid derivatives |
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WO1996005233A1 (fr) * | 1994-08-11 | 1996-02-22 | Shiseido Co., Ltd. | Acide hyaluronique acetyle a faible poids moleculaire, emollient, et procedes d'obtention et de purification de cet acide |
US6673919B2 (en) * | 2001-03-30 | 2004-01-06 | Chisso Cororation | Chemically modified hyaluronic acid or salts thereof, and a process for producing thereof |
JP4323148B2 (ja) * | 2002-09-30 | 2009-09-02 | チッソ株式会社 | n−アルカノイル化ヒアルロン酸もしくはその塩およびその製造法 |
JP2007191396A (ja) * | 2005-01-07 | 2007-08-02 | Rohto Pharmaceut Co Ltd | 皮膚外用剤 |
EP1871389A2 (fr) * | 2005-04-01 | 2008-01-02 | Zymes, LLC | Enrichissement de la peau au moyen de coq 10 en tant que systeme d'administration |
RU2383341C2 (ru) * | 2007-11-29 | 2010-03-10 | Ольга Викторовна Кухарева | Способ омоложения кожи |
US20100098794A1 (en) * | 2008-10-17 | 2010-04-22 | Armand Gerard | Topical anti-wrinkle and anti-aging moisturizing cream |
JP5420601B2 (ja) | 2011-07-25 | 2014-02-19 | 株式会社日立ハイテクノロジーズ | 荷電粒子装置 |
FR2989001B1 (fr) * | 2012-04-06 | 2017-07-21 | Centre Nat Rech Scient | Microparticules et nanoparticules constituees de polysaccharides hydrophobises et d'une alpha-cyclodextrine |
TW201343190A (zh) * | 2012-04-17 | 2013-11-01 | Bioptik Tech Inc | 有關應用於保溼及除皺之皮膚保養組合成份 |
RU2524663C1 (ru) * | 2013-04-26 | 2014-07-27 | Общество с ограниченной ответственностью "ДЖИ-Групп" | Комплексное косметическое средство |
KR20150015209A (ko) * | 2013-07-31 | 2015-02-10 | 주식회사 피코테라 | 저분자 아세틸화 히알루론산의 제조방법 및 이의 용도 |
CN103505736A (zh) * | 2013-09-23 | 2014-01-15 | 天津大学 | 基于改性透明质酸的高分子脂质体及其制备方法 |
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2015
- 2015-02-27 FR FR1551711A patent/FR3033134B1/fr not_active Expired - Fee Related
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2016
- 2016-02-26 WO PCT/FR2016/050447 patent/WO2016135430A1/fr active Application Filing
- 2016-02-26 US US15/552,318 patent/US20180036220A1/en not_active Abandoned
- 2016-02-26 EP EP16710260.7A patent/EP3261613A1/fr not_active Withdrawn
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FR3033134B1 (fr) | 2018-05-04 |
WO2016135430A1 (fr) | 2016-09-01 |
FR3033134A1 (fr) | 2016-09-02 |
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