EP1631594A1 - Neuer wirkstoff zur stimulation der befreiung der beta-endorphine, kosmetische und/oder dermatologische zusammensetzungen die ihn enthalten und deren verwendungen - Google Patents

Neuer wirkstoff zur stimulation der befreiung der beta-endorphine, kosmetische und/oder dermatologische zusammensetzungen die ihn enthalten und deren verwendungen

Info

Publication number
EP1631594A1
EP1631594A1 EP03718827A EP03718827A EP1631594A1 EP 1631594 A1 EP1631594 A1 EP 1631594A1 EP 03718827 A EP03718827 A EP 03718827A EP 03718827 A EP03718827 A EP 03718827A EP 1631594 A1 EP1631594 A1 EP 1631594A1
Authority
EP
European Patent Office
Prior art keywords
rhamnose
molecule
polysaccharides
polysaccharide
endorphins
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Withdrawn
Application number
EP03718827A
Other languages
English (en)
French (fr)
Inventor
Sophie Leclere
Jean-François MOLINA
Laurent Lassalle
Jean-Luc Philbe
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Societe La Biochimie Appliquee SOLABIA SAS
Original Assignee
Societe La Biochimie Appliquee SOLABIA SAS
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Societe La Biochimie Appliquee SOLABIA SAS filed Critical Societe La Biochimie Appliquee SOLABIA SAS
Publication of EP1631594A1 publication Critical patent/EP1631594A1/de
Withdrawn legal-status Critical Current

Links

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
    • A61Q19/005—Preparations for sensitive skin
    • 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
    • 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
    • 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
    • A61Q17/04—Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
    • 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
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/20—Bacteria; Culture media therefor
    • C12N1/205—Bacterial isolates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P19/00—Preparation of compounds containing saccharide radicals
    • C12P19/04—Polysaccharides, i.e. compounds containing more than five saccharide radicals attached to each other by glycosidic bonds
    • 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
    • A61K2800/70—Biological properties of the composition as a whole
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
    • C12R2001/00—Microorganisms ; Processes using microorganisms
    • C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
    • C12R2001/22—Klebsiella

Definitions

  • New agent stimulating the release of ⁇ -endorphins cosmetic and / or dermatological compositions containing them and their applications.
  • the present invention relates to the field of basic necessities of life and more particularly to the fields of cosmetology, pharmacy and more specifically dermatology.
  • the present invention relates to active compounds stimulating the release of ⁇ -endorphins by keratinocytes, comprising repetitive saccharide sequences and containing at least one rhamnose molecule attached in a branched manner.
  • Rli is a rhamnose molecule
  • Rh * is a rhamnose molecule linked in a branched manner to the neighboring element
  • O is a molecule of a hexosidic or pentosidic sugar
  • U is a molecule of uronic acid and n is between 1 and 100, preferably from 5 to 65.
  • the present invention also relates to the use of compounds comprising repetitive saccharide sequences containing at least one molecule of rhamnose attached in a branched manner and preferably containing predominantly rhamnose, as cosmetic and / or pharmaceutical agent, in particular dermatological, stimulating the release of ⁇ - endorphins.
  • the present invention also relates to cosmetic and / or pharmaceutical compositions which contain at least one of these new active compounds, of formula I, optionally in combination or in mixture with one or more excipients or vehicles cosmetics and / or pharmaceuticals suitable for application to the skin, mucous membranes or integuments.
  • compositions relate in particular to the care and / or treatment of the skin, including the lips and integuments (nails, hair, hair, etc.).
  • ⁇ -endorphins are neuropeptides derived from the pro-opiomelanocortin (POMC) precursor and have already been the subject of numerous studies published in the literature.
  • POMC pro-opiomelanocortin
  • keratinocytes are both sensitive to many neuromediators, in particular to ⁇ -endorphins, synthesized by nerve cells or by other epidermal cells, but are also capable of synthesizing them. This particular link between nervous and epidermal tissues could be explained by their common ectoblastic embryonic origin.
  • the ⁇ -endorphins synthesized by the skin represent more than 50% of the rate of circulating endorphins and are therefore particularly advantageous for attenuating or eliminating painful phenomena.
  • ⁇ -endorphins can be triggered in response to numerous signals, in particular in response to cellular stress, to the secretion of other mediators themselves induced by stress (IL-1, IL-6, TNF, etc. ..) or following significant physical effort.
  • IL-1, IL-6, TNF, etc. .. other mediators themselves induced by stress
  • IL-6 IL-6, TNF, etc. ..
  • other mechanisms of cellular release of ⁇ -endorphins exist in the absence of cellular stress.
  • ⁇ -endorphins are chemical analgesics naturally produced by the body which, by interacting with opiate receptors, bring the body a feeling of well-being. This sensation is accompanied by an immunomodulatory effect.
  • ⁇ -Endorphins are also responsible for the initiation of a number of biological reactions that manifest themselves at all levels of the body, for example, by stimulation of the vascular and cardiac system, or by muscle relaxation.
  • neuromediators thus constitute real “pleasure” molecules because their release is accompanied by a soothing or relieving effect, locally and generally.
  • the Applicant has unexpectedly discovered that polysaccharides and their derivatives, comprising saccharide repeating sequences containing at least one molecule of rhamnose attached in a branched manner, have the property of stimulating the cutaneous release of ⁇ -endorphins.
  • biological activities immunomodulation, anti-inflammation
  • oligosaccharides of 2 to 6 sugars containing at least two galactose units in particular those extracted from the Tephrosia plant in a cosmetic and / or dermatological composition to stimulate the release of ⁇ -endorphins from the skin.
  • new polysaccharides have been identified, quite unexpectedly, capable of stimulating, without cellular stress, the secretion of ⁇ -endorphins by keratinocytes.
  • These new cosmetic and / or dermatological agents are, unlike the prior art, made up of repeating elements containing at least one molecule of rhamnose attached in a branched manner, and preferably containing predominantly rhamnose which, in addition, their confer a high affinity for keratinocytes.
  • Rhamnose was also known for its ability to limit the biological phenomena leading to allergy of the immune type (patent FR-A1 -2756735) or used, in free form, obtained after hydrolysis of exopolysaccharides, as a flavoring agent or as flavorings (patent FR-A 1-2624522).
  • patent FR-A1 -2756735 a flavoring agent or as flavorings
  • none of these studies previously carried out on rhamnose made it possible to predict such a stimulating effect of rhamnose in the form attached in a branched manner to a saccharide chain, on the cutaneous secretion of endorphins.
  • the new active ingredients are characterized in that the repeating elements, mainly containing rhamnose, comprise at least the components of general formula I:
  • Rh is a molecule of rhamnose
  • Rh * is a molecule of rhamnose attached in a branched manner
  • O is a molecule of a hexosidic or pentosidic sugar
  • U is a molecule of uronic acid and n is between 1 and 100, preferably between 5 and 65.
  • the term “derivatives” groups together the hydrolysis products of the polysaccharides and also the sugar derivatives obtained by chemical modification of the structure of the saccharides according to the invention.
  • the derivative molecule to be active on the secretion of ⁇ -endorphins it is however necessary that the rhamnose branching and / or the rhamnose molecule attached in a ramified manner to the saccharide chain are not globally altered by the chemical reactions in order that the branched rhamnose remains accessible.
  • the rhamnose molecule initially in the branched position can quite, following a chemical modification, be located in the terminal position of the derivative molecule.
  • the new derivatives are defined as any compound of saccharide nature as long as it contains at least one accessible rhamnose molecule located at the end of the chain or branched and consists mainly of rhamnose.
  • the new derivatives according to the invention then have the same structure and / or are derived from the new polysaccharide according to the invention, which leads to compounds for which n has a lower value. It can therefore particularly be oligosaccharide hydrolysis products.
  • These hydrolysates or fractions can in particular be obtained from a polysaccharide of higher molecular weight, by known degradation techniques, in particular by enzymatic hydrolysis or chemical hydrolysis.
  • the sugar derivatives obtained by chemical modification can be amino, acid derivatives and saccharide salts and / or predefined hydrolysis products.
  • Sugar O can in particular be chosen from fucose, galactose, ribose, arabinose, xylose and mannose.
  • uronic acid U is meant any hexose oxidized on its primary alcohol function to carboxylic acid, in particular glucuronic acid, galacturonic acid, mannuronic acid or iduronic acid
  • the branched rhamnose molecule can be fixed by an osidic bond from its carbon 1 to a free carbon of a sugar O or uronic acid U or Rh rhamnose molecules.
  • the saccharide chain in particular on carbons 2 or 3.
  • the repeating elements can in particular consist of the sequence of general formula II:
  • Rh is a molecule of rhamnose
  • O is a molecule of a hexosidic or pentosidic sugar
  • U is a molecule of uronic acid
  • the ramification of rhamnose on the osm O is done according to an osidic bond (1 ⁇ 2) or (l- ⁇ 3).
  • the sugar O is galactose and the uronic acid U is glucuronic acid.
  • the sequence has a sequence containing 3 molecules of rhamnose, one of which is branched, 2 molecules of galactose and one molecule of glucuronic acid.
  • a particularly advantageous polysaccharide according to the invention has been identified and is presented in Example 1. According to formula II, n represents a value such that this polysaccharide has a molecular weight of the order of 50,000 daltons.
  • this polysaccharide has the rhamnose branching on the galactose in position V. It appears from the analyzes presented in Example 1 that this polysaccharide is more particularly made up of the following repeating unit: ⁇ 4) - ⁇ -L-Rha /? (l ⁇ 3) - ⁇ -D-Gal ⁇ (l- ⁇ 2) - ⁇ -L-Rha /?
  • repeating elements can in particular consist of the sequence of general formula III:
  • the sugar O is glucose and the uronic acid U is glucuronic acid, preferably according to a sequence containing 3 molecules of rhamnose including one branched, one molecule of glucose and one molecule of acid glucuronic.
  • Such a polysaccharide can in particular be obtained according to the method described below from a culture of bacteria of the Klebsiella planticola type, in particular the strain 1-2743 (N ° CNCM I-2743 - National Collection of Culture of Microorganisms).
  • this polysaccharide as described in Example 2 and called BEC291, has the rhamnose branching on the rhamnose in position III. It appears from the analyzes presented in Example 2 that this polysaccharide more particularly consists of the following repeating unit: ⁇ 3) - ⁇ -L- Rha /? (L ⁇ 4) - /? - D-Glcp (l ⁇ 2) - [ ⁇ -L-Rha /? (L ⁇ 3)] - -L-Rha (1 ⁇ 4) - ⁇ -D-Glc /? A ( ⁇ ⁇ - -
  • this polysaccharide also makes it possible to obtain a mixture of fractions of lower molecular weight, in particular the majority fraction of 5,000 daltons, optionally purifiable and particularly advantageous according to the invention.
  • the polysaccharides or saccharide derivatives can be of bacterial or vegetable origin, ... They can be obtained by conventional techniques for producing polysaccharides (chemical synthesis, enzymatic extraction of exopolysaccharides, etc.).
  • the polysaccharides are exopolysaccharides obtained by fermentation of a bacterial strain by producing, of the encapsulated bacteria type, according to a production process such as that detailed in patent FR-B 1-264522.
  • This process is defined in that a strain of Klebsiella type bacteria is cultured in a nutritive medium comprising a carbon source, a preferential nitrogen source and appropriate mineral salts, at a pH of approximately 6 to 8 , at a temperature of about 30 to 35 ° C, with stirring and aeration, for 4 to 12 days.
  • the carbon / nitrogen ratio is advantageously greater than 5 in order to promote the secretion of the polysaccharide.
  • the polysaccharide can then be isolated by subjecting the fermentation at a heat treatment at approximately 70-120 ° C, for 10 minutes to approximately 1 hour, then separating it, for example by centrifuging in the cold.
  • Exopolysaccharides and cellular polysaccharides are found entirely in the clear supernatant phase. If necessary, the polysaccharides can be purified by precipitation by adding a non-solvent organic liquid such as acetone or a lower alcohol such as ethanol or propanol, and separated by filtration or centrifugation before being dried.
  • a non-solvent organic liquid such as acetone or a lower alcohol such as ethanol or propanol
  • the isolated polysaccharides can thus easily be incorporated into a composition, as such or in hydrolyzed form.
  • the hydrolysis can be carried out before drying by common methods such as acid hydrolysis. It can be carried out using a proton donor usually used, such as hydrochloric acid, at a temperature ranging from 50 to 100 ° C. and for 30 minutes to 4 hours, depending on the desired size of the fractions.
  • a proton donor usually used such as hydrochloric acid
  • This protocol can be carried out using bacterial strains producing exopolysaccharides rich in rhamnose, in particular encapsulated bacteria.
  • a strain of Klebsiella bacteria preferably Klebsiella pneumoniae or Klebsiella planticola, is used.
  • polysaccharide alone or a mixture of heterogeneous polysaccharides and / or a mixture of their derivatives.
  • polysaccharides alone and / or the mixture of polysaccharides and / or their derivatives can also, in the context of the invention, be used as active ingredient in grafted form, in particular by chemical substitution means on the free carboxylic function uronic acid U, on a chemical, biochemical or biological residue which does not modify the stimulating effect of the secretion of ⁇ -endorphins.
  • they may be fatty chains containing from 6 to 30 carbon atoms or chains of amino acids. It is also possible to incorporate polysaccharides and / or their derivatives according to the invention in a cyclodextrin.
  • polysaccharides and / or their derivatives according to the invention have other remarkable properties, in particular of inhibition of the cellular adhesion of neutrophils to keratinocytes (40% inhibition at 2% of the compound described in Example 1) and have a very good affinity for keratinocytes, at least equal to that of rhamnose (60% inhibition of neoglycoprotein binding obtained with 8% of the compound described in Example 1). These two properties have been demonstrated in particular in Examples 4 and 5.
  • polysaccharides and / or their derivatives previously defined are therefore particularly suitable for use as a cosmetic and / or pharmaceutical and more particularly dermatological agent, in particular for stimulating the cutaneous release of ⁇ -endorphins.
  • a subject of the invention is therefore also cosmetic and / or pharmaceutical and in particular dermatological compositions comprising, as active principle, at least one polysaccharide compound and / or a derivative as defined above, optionally in combination or in mixture with a or more suitable cosmetic and / or pharmaceutical excipients or vehicles.
  • Said polysaccharides and / or derivatives can be incorporated into these compositions at a concentration varying between 0.001% and 20% by weight, and preferably between 0.01% and 10% by total weight of the composition.
  • the composition contains, as active principle, Rhamnosoft ® polysaccharide of Example 1 and / or BEC291 polysaccharide of Example 2.
  • compositions according to the invention may be in any form suitable for skin application, in particular in the form of a gel, of an emulsion, for example, an oil-in-water or water-in-oil emulsion, or in the form of a multiple emulsion, with liquid crystals or not. They can also be in the form of aqueous solution, lotion, milk, cream, mask, foam. It is also possible to use them in the form of patches.
  • the composition can also comprise the usual acceptable pharmaceutical and / or cosmetic excipients.
  • these excipients mention may in particular be made of sun protection agents, in particular for carrying out sun care, hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic active agents, gums, resins, surfactants, solvents, fillers such as as rice starch, pigments, preservatives, essential oils, antioxidants, dyes, pigments, pearlescent agents, glitter, perfumes, odor absorbers, pH regulating agents or neutralizing agents, penetrating agents, thickening agents, such as those usually used.
  • sun protection agents in particular for carrying out sun care, hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic active agents, gums, resins, surfactants, solvents, fillers such as as rice starch, pigments, preservatives, essential oils, antioxidants, dyes, pigments, pearlescent agents, glitter, perfumes, odor absorbers, pH regulating agents or neutralizing agents, penetrating agents, thick
  • the choice and / or the quantity of the ingredients complementary to the composition will naturally be determined by the choice of physical properties and of the desired consistency for the composition according to the invention.
  • the various adjuvants are used in proportions conventionally used in the field of cosmetics, namely for example from 0.01 to 20% of the total weight of the composition, the complement being constituted by a vehicle such as water or a water-alcohol mixture .
  • ⁇ -endorphins may also be incorporated in the composition according to the invention, including cocoa extract commercialized under the name ® Caobromine (CEP).
  • CEP Caobromine
  • the composition may also contain a second compatible active principle, in particular for dermatological use, in order to confer a double property on the composition or in order to limit the uncomfortable sensations linked to the application of this second active principle.
  • a second compatible active principle in particular for dermatological use, in order to confer a double property on the composition or in order to limit the uncomfortable sensations linked to the application of this second active principle.
  • active principles mention may in particular be made of local antiseptics such as benzoyl peroxide, local anti-acne drugs such as tretinoin, a local antibiotic such as sulfacetamide to reduce the side effects of local irritation, a local anti-inflammatory such as ibuprofen.
  • the second active ingredient is added to the composition in a usually effective therapeutic amount.
  • composition according to the invention can be produced in a conventional manner, according to the known methods usually used in the field of cosmetology and / or dermatology.
  • the compositions can be used for daily care and / or treatment and / or protection of the skin of the body and / or of the face and / or the integuments (nails, hair, hair, etc.).
  • these compositions By stimulating the production of ⁇ -endorphins, these compositions have soothing and calming properties, in particular skin discomfort which may result, for example, from irritations, aggressions of the skin, in particular by external agents such as certain therapeutic treatments. , climatic agents (wind, cold, sunburn, etc.), waxing, shaving, insect bites ... and thus provide a feeling of well-being. They can therefore be particularly used for the care of sensitive or sensitized skin.
  • compositions also provide a local analgesic effect and can also be used in the pharmaceutical and more particularly dermatological field to relieve skin and / or subcutaneous pain, to suppress the unpleasant perception of skin reactions, the feelings of discomfort. the skin which manifests itself in particular in the case of allergies, pruritus, itching, insect bites.
  • a subject of the invention is therefore also the use of the polysaccharide agents according to the invention for the production of a medicament intended to relieve skin and / or subcutaneous pain, and / or to suppress the sensations of discomfort of the skin (allergies, pruritus, irritations, skin pain linked to burns, stings, chapping, cuts ...) by local application.
  • the invention also relates to a cosmetic care process comprising the application to an affected area of the skin and / or integuments of at least one active compound previously defined in a cosmetically acceptable excipient or optionally in the form of one of the cosmetic compositions previously defined.
  • compositions according to the invention have no toxicity and do not cause any local intolerance. They are also not allergenic.
  • Example 1 Example of the structure of the repeating unit of the exopolysaccharide produced by Klebsiella pneumoniae 1-714 and called Rhamnosoft ® :
  • the composition of Rhamnosoft ® was studied by the analysis procedure by GC gas chromatography and by gas chromatography coupled with mass spectrometry (GC / MS) of the degradation products after permethylation of the native molecule.
  • the method of degradation of uronic acids by ⁇ -elimination after permethylation was used in particular to confirm the position and the nature of the substituents of the galactose residue.
  • the Rhamnosoft sequence was determined by nuclear magnetic resonance (NMR).
  • this polymer With a branched structure, this polymer with a molecular weight of the order of 50,000 daltons therefore has a saccharide sequence comprising three molecules of rhamnose (I, III, VI), two molecules of galactose (II, V), one molecule of acid glucuronic (IV). Rhamnose therefore constitutes 50% of the polysaccharide.
  • the polysaccharide has a rhamnose VI branch on the galactose in position V.
  • the structure of the repeating unit is in this case:
  • Example 2 Example of the structure of the repeating unit of the exopolysaccharide produced by Klebsiella planticola 1-2743 and called BEC 291:
  • the composition of BEC 291 was studied by the analysis procedure by GC gas chromatography and by gas chromatography coupled with mass spectrometry (GC / MS) of the degradation products after permethylation of the native molecule.
  • GC / MS gas chromatography coupled with mass spectrometry
  • the method of degradation of uronic acids by ⁇ -elimination after permethylation was used.
  • the BEC 291 sequence was determined by nuclear magnetic resonance (NMR).
  • this polymer therefore has a saccharide sequence comprising three molecules of rhamnose (I, III, V), a molecule of glucose (II), a molecule of glucuronic acid (IV).
  • This polysaccharide therefore has a rhamnose V branch on the rhamnose in position III.
  • the structure of the repeating unit in this case is:
  • Example 3 Study of the effect of the polysaccharides according to the invention containing 50% of rhamnose on the release of ⁇ -endorphins by the keratinocytes.
  • ⁇ Procedure Normal human keratinocytes are cultured for 48 hours. They are treated for 36 hours with the product to be tested. The supernatants, containing ⁇ -endorphin, are collected and stored at -20 ° C until assay. The control of the test is carried out by treating the keratinocytes with the excipient (butylene glycol 70%) at 2%. The assay is carried out with an ELISA kit (spectrophotometric assay at 450 nm). The results are expressed in programs per milliliter of synthesized ⁇ -endorphin. Prior cytotoxicity studies were systematically carried out in these examples in order to show that the effects of the product are not linked to a cytotoxic effect.
  • Rhamnosoft ® is tested at concentrations of 1% and 5%.
  • the hydrolyzed fractions of Rhamnosoft ® of 13 kdaltons and 5 kdaltons are mainly obtained during the acid hydrolysis of Rhamnosoft "carried out in the presence of hydrochloric acid at a concentration of the order of 0.1 to 2.5 mol / liter, at a temperature from 50 to 100 ° C for 30 minutes and 4 hours respectively. They can be purified if necessary by ethanolic precipitation or by physical methods.
  • BEC 291 has been tested at concentrations of 0.001% and 0.02%
  • polysaccharide BEC291 also has the capacity to stimulate the release of ⁇ -endorphins by human keratinocytes. Preliminary studies have demonstrated the absence of cytotoxicity with respect to keratinocytes, regardless of the concentrations of BEC 291. Here again, the effect of the polysaccharide BEC 291 on the secretion of ⁇ -endorphins is not due to cellular stress but indeed an interaction between the saccharide fractions and the keratinocyte receptors.
  • FrBEC 291 hydrolyzed fraction of BEC 291 of 5 kd.
  • This FrBEC291 fraction is mainly obtained by acid hydrolysis of BEC 291, carried out in the presence of hydrochloric acid at a concentration of the order of 0.1 to 2.5 mol / liter, at a temperature of 50 ° C to 100 ° C for 4 hours.
  • Example 4 Study of the affinity of keratinocytes with respect to polysaccharides according to the invention containing 50% of rhamnose.
  • NGP fluorescent neoglycoproteins
  • Experiment 2 Experiment 1 was repeated in the presence of Rhamnosoft ® in order to determine its inhibitory effect on the binding of fluorescent NGPs on human keratinocytes. To do this, human keratinocytes were pre-incubated for 15 min with different concentrations of Rhamnosoft ® . At the end of this period, the fluorescent NGPs were added to the concentration of 100 ⁇ g / ml and experiment 1 was "renewed.
  • Experiment 3 The specific binding of Rhamnosoft ® to human keratinocytes was studied by the technique of labeling Rhamnosoft ® with a fluorescent derivative and by the technique of fixing fluorescent latex beads impregnated with Rhamnosoft ".
  • Rhamnosoft ® has everything First marked with fluorine escheine isothiocyanate (FTC). Human keratinocytes were incubated in the presence of Rhamnosoft "thus polymerized, at different concentrations ranging in particular from 0.025% to 0.4%. Binding was determined by measuring the index fluorescence and binding obtained for a concentration of 0.4% of Rhamnosoft ® -FTC was visualized by fluorescence microscopy BioRad MRC1025 at 488nm and 520nm and phase contrast. The technique using latex beads was carried out using 0.2 ⁇ m diameter Polysciences latex beads in activated -COOH form.
  • FTC fluorine escheine isothiocyanate
  • Keratinocytes were incubated for 30 min at 37 ° C in the presence of beads on which Rhamnosoft ® was immobilized. The cells are then washed and fixed with paraformaldehyde (1% w / v in PBS) for 30 minutes at 20 ° C. The results were visualized using a Biorad MRC1025 fluorescence microscope at 488nm and 520nm and in phase contrast.
  • polysaccharide according to the invention binds specifically on the membrane receptors of human keratinocytes with a particularly high affinity.
  • the keratinocytes were pre-incubated for 24 hours in the presence of Rhamnosoft ® at different concentrations and in the presence of 3 ⁇ g / ml of lipopolysaccharides (LPS). Human neutrophils previously made fluorescent by treatment with calcein are then added. After 2 hours of contact, the keratinocytes are washed and lysed. The inhibition of neutrophil adhesion is determined by measuring the fluorescence index.
  • LPS is an agent that induces inflammation.
  • polysaccharide according to the invention induces an inhibition of the cellular adhesion of neutrophils to keratinocytes.
  • Example 6 Examples of cosmetic formulations according to the invention.
  • Example 7 Examples of dermatological formulations according to the invention.
  • Anti-mosquito wellness ointment
EP03718827A 2003-02-04 2003-02-04 Neuer wirkstoff zur stimulation der befreiung der beta-endorphine, kosmetische und/oder dermatologische zusammensetzungen die ihn enthalten und deren verwendungen Withdrawn EP1631594A1 (de)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/FR2003/000330 WO2004078789A1 (fr) 2003-02-04 2003-02-04 Nouvel agent stimulant la liberation des beta-endorphines, compositions cosmetiques et/ou dermatologiques en contenant et leurs applications

Publications (1)

Publication Number Publication Date
EP1631594A1 true EP1631594A1 (de) 2006-03-08

Family

ID=32947085

Family Applications (1)

Application Number Title Priority Date Filing Date
EP03718827A Withdrawn EP1631594A1 (de) 2003-02-04 2003-02-04 Neuer wirkstoff zur stimulation der befreiung der beta-endorphine, kosmetische und/oder dermatologische zusammensetzungen die ihn enthalten und deren verwendungen

Country Status (2)

Country Link
EP (1) EP1631594A1 (de)
WO (1) WO2004078789A1 (de)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2853539B1 (fr) * 2003-04-08 2007-10-19 Ind E Com De Cosmeticos Natura COMPOSITION COSMETIQUE COMPRENANT LE FROPs ET LE RROPS, ET SON UTILISATION EN COSMETIQUE POUR UNE ACTION ANTI-VIEILLISSEMENT CUTANEE
FR2876283A1 (fr) * 2004-10-07 2006-04-14 Ind E Com De Cosmeticos Natura Composition cosmetique comprenant un compose saccharidique presentant un motif repete riche en rhamnose, et son utilisation en cosmetique pour une action anti- vieillissement cutane
FR2986966B1 (fr) * 2012-02-17 2014-03-21 Biochimie Appliquee Soc Composition cosmetique et/ou dermatologique contenant des activateurs de sirtuines
FR2989274B1 (fr) * 2012-04-12 2016-02-26 Biochimie Appliquee Soc Composition cosmetique cutanee et/ou dermatologique destinee a limiter l'adhesion des bacteries pathogenes au niveau de la peau
CN104403981A (zh) * 2014-12-18 2015-03-11 湖北工业大学 一种新型胞外多糖及其生产菌株和制备方法
PT3658160T (pt) * 2017-07-28 2021-08-26 Isdin Sa Utilização de ramnose e seus derivados como agentes antifúngicos
FR3090362B1 (fr) * 2018-12-20 2021-01-08 Oreal Composition comprenant un polysaccharide, un polyol, ainsi qu’un ester et une huile particuliers
FR3090360B1 (fr) * 2018-12-20 2021-01-15 Oreal Composition comprenant un polysaccharide, un polyol et un ester spécifique
WO2021255255A1 (en) * 2020-06-19 2021-12-23 L'oreal Composition comprising a polyol, a polyglycerol ester, a hyaluronic acid salt and a specific hydrophilic polymer
FR3111555B1 (fr) * 2020-06-19 2022-09-30 Oreal Composition comprenant un polysaccharide, un polyol et au moins un ester polyglycérolé
FR3111546B1 (fr) * 2020-06-19 2023-04-07 Oreal Composition comprenant un polyol, un ester de polyglycérol, un sel d’acide hyaluronique et un polymère hydrophile spécifique

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2624522B1 (fr) * 1987-12-11 1990-03-09 Bioeurope Culture d'un micro-organisme du genre klebsiella sp., et procede de production d'un melange d'oses a teneur elevee en rhamnose mettant en oeuvre cette culture
US5989874A (en) * 1995-03-27 1999-11-23 Tayca Corporation Humectant, antistatic agent, dispersant and film-forming agent having polysaccharide as active principle, preparation process of polysaccharides, and Kliebsiella ocytoca TNM-3 strain
WO1996039155A1 (fr) * 1995-06-05 1996-12-12 Tayca Corporation Immunostimulant
FR2811228B1 (fr) * 2000-07-07 2002-10-25 Lvmh Rech Utilisation d'oligosaccharides ou d'extraits de plantes en contenant comme agent cosmetique ou dermatologique notamment pour stimuler la production de beta-endorphine dans la peau

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2004078789A1 *

Also Published As

Publication number Publication date
WO2004078789A1 (fr) 2004-09-16

Similar Documents

Publication Publication Date Title
EP1090629B1 (de) Kombination aus Aescin und Dextran Sulphat
EP0892642B1 (de) Verwendung eines extraktes mindestens einer in vitro kultivierten labiate der gattung rosmarinarus in einer zusammensetzung
FR2842201A1 (fr) Nouvel oligosaccharide, compositions cosmetiques et/ou dermatologiques en contenant et ses applications
EP1763355B1 (de) Zusammensetzung enthaltend D-Mannoheptulose und/oder Perseitol zur Behandlung oder Vorbeugung von Krankheiten, die mit einer Veränderung der angeborenen und/oder erworbenen Immunität verbunden sind
FR2715565A1 (fr) Composition cosmétique ou dermatologique stabilisée contenant plusieurs précurseurs d'un même actif pour maximaliser sa libération, son utilisation.
EP2303300B1 (de) Zusammensetzungen zur förderung der entwicklung und des wachstums einer günstigen vaginalen mikroflora
WO2008148967A2 (fr) Preparations pharmaceutiques ou cosmetiques pour application topique et/ou parenterale, leurs procedes de preparation, et leurs utilisations
CA2209695C (fr) Utilisation d'un polyholoside dans une composition destinee a favoriser la desquamation de la peau, et composition le comprenant
EP0818201B1 (de) Verwendung eines Polysaccharids zur Stimulierung der Immunabwehr
CA2550671C (fr) Procede d'innoformulation d'une base galenique biocompatible
EP0909556B1 (de) Rosaceae extrakt als bradykinin-antagonist
EP1278532B1 (de) Extrakt aus einer pflanze der spezies olea europaea als inhibitor der no-synthase und verwendungen
EP1631594A1 (de) Neuer wirkstoff zur stimulation der befreiung der beta-endorphine, kosmetische und/oder dermatologische zusammensetzungen die ihn enthalten und deren verwendungen
EP1530480B1 (de) Kosmetische zusammensetzung mit monosacchariden oder polysacchariden, anwendungen und behandlungsverfahren
CA2255226C (fr) Utilisation de l'acide cinnamique ou d'au moins l'un de ses derives dans une composition cosmetique
CA2186775C (fr) Fraction ribosomale et composition la contenant
FR3055550B1 (fr) Nouvel actif immunomodulateur et composition le comprenant
FR3086170A1 (fr) Formulation cosmetique
FR3016291B1 (fr) Composition comprenant au moins un monosaccharide et un extrait de bacterie filamenteuse
CA2353677A1 (fr) Utilisation d'au moins un extrait d'au moins une iridacee dans une composition destinee a stimuler les defenses immunitaires
FR2837388A1 (fr) Utilisation d'un polysaccharide comme agent filmoprotecteur, compositions cosmetiques et/ou dermatologiques en contenant et procede de soins cosmetiques le mettant en oeuvre
WO2023186353A1 (fr) Dextrines hyperbranchees pour leur utilisation topique pour la prevention ou le traitement d'au moins un symptome de l'inflammation cutanee
EP1620185A2 (de) Kosmetische oder pharmazeutische zusammensetzung enthaltend säureamide und deren dermatologische verwendung
FR2720646A1 (fr) Extrait de glumes d'avoine, son procédé de préparation et son utilisation en thérapie et/ou en cosmétique.
WO2005039523A1 (fr) Composition comprenant une lactone sesquiterpenique

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20050908

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LI LU MC NL PT SE SI SK TR

17Q First examination report despatched

Effective date: 20090206

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20090617