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EP0979065A1 - Use of oligosaccharides for the treatment of connective tissues - Google Patents

Use of oligosaccharides for the treatment of connective tissues

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Publication number
EP0979065A1
EP0979065A1 EP98914000A EP98914000A EP0979065A1 EP 0979065 A1 EP0979065 A1 EP 0979065A1 EP 98914000 A EP98914000 A EP 98914000A EP 98914000 A EP98914000 A EP 98914000A EP 0979065 A1 EP0979065 A1 EP 0979065A1
Authority
EP
European Patent Office
Prior art keywords
oligosaccharide
derivative
galactose
melibiose
terminal position
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Withdrawn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
EP98914000A
Other languages
German (de)
English (en)
French (fr)
Inventor
Alexandre Michel Robert
Ladislas Robert
Dominique Castelli
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.)
Johnson and Johnson Consumer Holdings France SAS
Original Assignee
Johnson and Johnson Consumer France 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 Johnson and Johnson Consumer France SAS filed Critical Johnson and Johnson Consumer France SAS
Publication of EP0979065A1 publication Critical patent/EP0979065A1/en
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7016—Disaccharides, e.g. lactose, lactulose
    • 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
    • A61K31/702—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/60—Sugars; Derivatives thereof
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • 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

Definitions

  • the present invention relates to new uses of a class of oligosaccharides and their derivatives. It also relates to a cosmetic method which makes it possible to increase the glycosaminoglycan (GAG) content of connective tissues and to combat free radicals.
  • GAG glycosaminoglycan
  • the cohesion of the fibrous network of the connective tissues is effected by proteoglycans such as decorin and biglycan.
  • proteoglycans such as decorin and biglycan.
  • the hydration and viscoelasticity of the tissues is largely attributable to hyaluronan, a glycosaminoglycan of high molecular weight (of the order of a million).
  • this glycosaminoglycan (GAG) binds, via specific interactions (GAG- containing protein), a large number of aggrecan molecules which thus form very high molecular weight aggregates, imparting both hydration, resistance and elasticity to these tissues.
  • Hyaluronan is synthesized by means of hyaluronan synthetase, an enzyme located in the cell membrane.
  • the hyaluronan synthesized surrounds the cell and thus regulates the movement of molecules in its vicinity, its migration, its association with other cells and macromolecules. Its degradation is effected by hyaluronidase, present in the testicles; similar enzymes (endogly- cosaminidases and endoglycuronidases) occur in the lysosomes, where the intracellular degradation of hyaluronan takes place after its endocytosis mediated by specific receptors.
  • hyaluronan is very sensitive to attack by free radicals, which rapidly degrade it. This mechanism, coupled with the fall in synthesis, is the one which explains its progressive loss with age. For all these reasons, the stimulation of its biosynthesis, as well as its protection against free-radical degradation, are of great importance.
  • the subject of the present invention is the use of an oligosaccharide possessing from 2 to 6 glycoside residues and having a galactose residue in a non-reducing terminal position, or of a derivative of such an oligosaccharide capable of being obtained by attachment of a hydrophobic radical, for the preparation of a composition intended for increasing the synthesis and/or decreasing the degradation of the proteoglycans of connective tissue.
  • these oligosaccharides are useful for increasing the synthesis and/ or decreasing the degradation of glycosaminoglycans (GAGs), especially hyaluronan or hyaiuronic acid.
  • GAGs glycosaminoglycans
  • Proteoglycans consist of a protein moiety combined via covalent bonding with a specific polysaccharide structure: glycosaminoglycans (GAGs); this polysaccharide fraction represents more than 95% of the total mass of the proteoglycan.
  • GAGs glycosaminoglycans
  • the polymerization of the disaccharide basic unit takes place via a ⁇ ( 1-4) bond.
  • the classification of GAGs is based on the nature of the sugars of the disaccharide monomer, as well as on the number and position of the sulphate groups attached to the molecule.
  • GAGs comprise, in particular, hyaiuronic acid, chondroitin sulphates, dermatan sulphate, keratan sulphate and heparan-sulphate proteoglycans, as well as heparin.
  • Oligosaccharides which are especially suitable for the preparation of a composition according to the invention are chosen from the group consisting of melibiose, lactose and their derivatives which can be obtained by attachment of a hydrophobic residue.
  • the hydrophobic residue is preferably chosen from linear or branched Ci-Cis alkyls, Ci-Cis alkylamines, saturated or unsaturated, linear or branched Ci-Cis carboxylic acids which are optionally substituted, linear or branched Ci-Cis primary, secondary or tertiary amides and Ci-Cis arylalkyls.
  • oligosaccharide derivatives suitable for carrying out the invention can belong, in particular, to one of the categories mentioned below, in which the oligosaccharide corresponds to the following general formula: galactose-n ( ⁇ or ⁇ ) - (Hex) p in which n represents position 1 , 2, 3, 4 or 6,
  • Hex represents a pentose or a hexose linked in ⁇ or ⁇ fashion, p is a number between 1 and 5; a) glycosides corresponding to the formulae:
  • R (CH2J..1, m being between 2 and 10, b) an acylated glycosylamine according to one of the following formulae, in which the oligosaccharide is preferably lactose, melibiose or stachyose:
  • R (CH )m, m being between 2 and 8, c) an alkylamine acylated with an aldonic acid obtained by oxidation of an oligosaccharide
  • the oligosaccharide or its derivative as defined above will be used for the preparation of a composition containing, in addition, cosmetically or pharmaceutically acceptable excipients suitable for oral administration.
  • the oligosaccharide or its derivative as defined above will be used for the preparation of a composition containing, in addition, cosmetically or pharmaceutically acceptable excipients suitable for internal topical administration.
  • the oligosaccharide or its derivative as defined above will be used for the preparation of a composition containing, in addition, cosmetically or pharmaceutically acceptable excipients suitable for external topical administration.
  • oligosaccharides and more especially melibiose and its derivatives, stimulate the biosynthesis of giycoconjugates in general and more specifically of hyaluronan, by fibroblasts, and in particular old fibroblasts, at and above very low doses. They are hence capable of improving the turgor, hydration and cohesion of the connective tissues in general and of the skin in particular.
  • oligosaccharides possessing from 2 to 6 glycoside residues and having a galactose in a non-reducing terminal position, or hydrophobic derivatives as defined above will be used for the preparation of a composition intended for combating the effects of UV radiation, namely the skin aging induced by UV radiation, and in particular the effects of free radicals.
  • Free radicals are, by definition, neutral or charged chemical species which possess an unpaired electron. This "celibate electron” endows them with special chemical properties and a short lifetime. They are reaction intermediates which become stabilized by fusion or transfer, and can be the source of a chain reaction.
  • the superoxide anion 0 2 ", the hydroxyl radical OH ' and the nitric oxide radical NO- may be mentioned.
  • oligosaccharides according to the invention and more especially of melibiose, in relation to this can be explained, in particular, by two mechanisms, by which the invention is in no way limited.
  • radicals liberated are superoxide and nitric oxide, which can combine to form the toxic peroxynitrite anion.
  • the invention also relates to the use of oligosaccharides as defined above, and in particular of melibiose, as free radical scavengers.
  • these oligosaccharides are capable of exerting a favourable effect against the free-radical attack involved in the degradation of cells and macromolecules of the dermis. Confirmation of these results has been obtained using the effect of UV on the skin.
  • GPX glutathione peroxidase
  • the elastase activity which can be extracted from the skin increases under the effect of UV.
  • Two types of activity are found in the dermis: one of the metalloendopeptidase type originating from the fibroblasts and sensitive to EDTA, and the other, of leukocytic origin, a PMN serine protease which is not inhibited by EDTA.
  • Monocytes-macrophages also produce a metalloelastase.
  • Treatment with these active principles increases the body's, and more especially the skin's, defences against free radicals and decreases oxidative stress, as is evidenced by measurement of the corresponding markers.
  • Melibiose and its derivatives are especially effective, since they are only slightly degraded in the body which does not contain clivage enzyme (melibiase) which today would only have been detected in bacteria.
  • the subject of the invention is also a cosmetic treatment method for combating the effects of free radicals and /or for increasing the synthesis or decreasing the degradation of glycosaminoglycans in a mammal in good health, comprising the administration of at least one oligosaccharide possessing from 2 to 6 glycoside residues and having a galactose in a non-reducing terminal position, or of at least one derivative of the latter capable of being obtained by attachment of a hydrophobic radical.
  • this administration will be carried out on the skin, the mucosae or the exoskeleton.
  • the oligosaccharides according to the invention are also useful in compositions intended for combating alopecia, for improving the hydration of the skin and for improving the cutaneous microcirculation.
  • compositions according to the invention can take the form, in particular, of solutions, gels, lotions, creams, W/O or O/W emulsions or multiple-phase emulsions, or the form of liposomes or any vesicular form. They will be formulated in a manner known to a person skilled in the art with texturing agents, emulsifiers, •thickeners, preservatives, and the like.
  • the concentration of oligosaccharides, in particular of melibiose, in the compositions according to the invention will advantageously be between 0.01 and 10% w/w, and preferably between 1 and 4% w/w.
  • Figure LA Variation of the amount of hyaiuronic acid as a function of the melibiose concentration in the fibroblast extracellular medium at the 5th passage.
  • Figure B Variation of the amounts of hyaiuronic acid as a function of the melibiose concentration in the fibroblast extracellular medium at the 10th passage.
  • Figure l .C Variation of the amounts of hyaiuronic acid present in the fibroblast extracellular medium at the 15th passage.
  • Figure 2 Variation of the amounts of hyaiuronic acid present in the fibroblast extracellular medium at the 15th passage.
  • Figure 2. Variation of the amount of hyaiuronic acid in the fibroblast intracellular medium as a function of the melibiose concentration at the 5th passage.
  • Figure 2.B Variation of the amount of hyaiuronic acid in the fibroblast intracellular medium as a function of the melibiose concentration at the 10th passage.
  • Figure 2.C. Variation of the amounts of hyaiuronic acid in the fibroblast intracellular medium as a function of the melibiose concentration at the 15th passage.
  • Figure 3 Incorporation of [ 3 H]glucosamine into the total glycoconjugates in the intra- and pericellular compartment. Effect of increasing doses of melibiose. Abscissa: Melibiose concentration ( ⁇ g/ml). Ordinate: [ 3 H]Glucosamine incorporated into the glycoconjugates, expressed as cpm/ million cells.
  • Figure 4 Incorporation of [ 3 H]glucosamine into the total glycoconjugates in the extracellular compartment. Effect of increasing doses of melibiose.
  • Abscissa Melibiose concentration ( ⁇ g/ml).
  • Abscissa Melibiose concentration C: 0; M L 1 ( ⁇ g/ml) .
  • Figure 6 Incorporation of [ 3 H]glucosamine into hyaluronan in the fibroblast extracellular compartment. Effect of melibiose at a concentration of 1 ⁇ g/ml.
  • Abscissa Melibiose concentration C: 0; M L 1 ( ⁇ g/ml).
  • Figure 8 The figure shows the effect of treatment with the active principles on the selenium-containing glutathione peroxidase content of rats' skin.
  • the values are given in moles of enzyme per mg of fresh weight of skin, in the upper the results are shown as percentages, the values for the control skins having been taken as 100%.
  • Figure 9 The histogram in the figure shows as ordinates the elastase activity of the skins on both the control and the treated sides of 3 groups of rats. It is seen that, with the exception of the group treated with the excipient alone (No. 3), the treated sides
  • Example 1 Effect of melibiose on the amount of hyaluronan in fibroblast cultures
  • Hyaiuronic acid or hyaluronan is assayed by an
  • HN hyaluronectin
  • HA hyaluronan
  • the bound HN level is measured by the phosphatase activity.
  • HN is preincubated in the presence of HA, the binding of HN to the plate is inhibited.
  • the change in absorbance at 405 nm is proportional to the inhibition by the HA contained in the samples.
  • This technique possesses several advantages: it is specific, has high affinity (threshold of detection: 1 ⁇ g/1) and is fast (assay within the day).
  • hyaluronectin This comprises three main steps: extraction of hyaluronectin from lamb's brain by grinding and centrifugation; preparation of an HA-Sepharose 4 B column by attachment of HA ( 100 mg) to Sepharose (4 g) in the presence of carbodiimide
  • the HA-Sepharose gel is washed with 1 M NaCl and then with 1 M acetic acid at 4°C; the gel is thereafter - washed with 200 ml of 0.2 M glycine/HCl buffer pH 2, then 100 ml of 4 M guanidine and physiological saline; purification of HN by affinity on the HA-Sepharose 4 B column and coupling with alkaline phosphatase: this is performed on the extract obtained at the end of the first step, removing the contaminating HA-HN complex; after coupling to alkaline phosphatase (AP) in the presence of glutaraldehyde, the uncoupled AP is removed by gel filtration.
  • the assay of HA by the ELSA technique comprises 5 principal steps. 1. Preparation of reference HA
  • HA isolated from rooster comb has to be purified prior to its use. In effect, this HA is contaminated with proteins and proteoglycans.
  • the HA is dissolved in PBS ( 1 mg/ml).
  • the contaminating proteoglycans are removed by treatment with chondroitinase ABC
  • the sensitization step consists in adsorbing HA in the plates.
  • Commercial HA 1 mg/ml is dissolved in 0.1 M bicarbonate buffer, 0.2 g/1 azide, and 250 ⁇ l are then distributed in each well of the ELISA plate.
  • the plates are sensitized at least overnight at 4°C and can be stored for 1 month at + 4°C.
  • the hyaluronectin which may be contaminating the sample is removed by protease treatment (Proteus vulgaris type
  • the sample is diluted to 1/ 10 in a protease solution ( 1 mg/ml) in TBS/0.2 g azide/ 1 for 18 hours at 37°C.
  • the protease activity is denatured by heat (20 minutes at 100°C).
  • the inhibition of the binding of HN to the HA adsorbed on the plate is proportional to the HA added during the preincubation.
  • the HA/OD 405 nm ratio is linearized by expressing the HA concentration on a logarithmic scale.
  • the optical density which is proportional to the amount of HA to be assayed, varies relatively little for a large variation in HA. In order to increase the reliability, the assay is always carried out in duplicate at 3 different sample concentrations.
  • the intra-assay variation is less than 5% and the inter-assay variation varies from 10 to 15%.
  • the material is a culture of human skin fibroblasts.
  • the source skin came from a 13-year-old child, and was removed during plastic surgery for resetting of the ears.
  • These cells are cultured on the basis of 3 x 10 5 cells per dish (nunc, 6 cm in diameter) in 5 ml of DMEM medium with 10% of foetal calf serum, 1% of penicillin/ streptomycin and 1% of fungizone, in a humid atmosphere containing 5% of C0 2 and at
  • Melibiose is added to the medium at different concentrations: 0.1 ⁇ g/ml, 1 ⁇ g/ml and 5 ⁇ g/ml final ( 1 ⁇ g/ml 3 ⁇ M).
  • the assays are carried out with cells from different passages, the dilution ratio (split ratio) being 1 /2: a young or early passage: 5th passage or cell population doubling (CPD); a medium-term passage: 10th passage; - a more advanced passage: 15th passage. 2 - Results
  • Figures 1 and 2 show the effect of increasing concentrations of melibiose on the amount of hyaluronan assayed in the culture medium and in the pericellular layer of the fibroblasts.
  • Example 2 Effect of melibiose on the biosynthesis of glycoconjugates - glycoproteins and glycos aminoglycans - in fibroblast cultures 1 - Materials and Methods
  • the material used is a culture of human skin fibroblasts.
  • Melibiose is added to the culture medium at different concentrations: 0.1 ⁇ g/ml, 1 ⁇ g/ml and 5 ⁇ g/ml final.
  • the assays are carried out with cells from two different passages, the dilution ratio (split ratio) being 1 /2: an early passage: 5th passage or cell population doubling (CPD); - a later passage: 15th passage.
  • Glucosamine is an amino sugar which participates in the composition of three families among the 4 main families of macromolecules of the extracellular matrix which possess glycanic chains, namely the collagens, the structural glycoproteins, the proteoglycans and the glycosaminoglycans (GAG chains), and in particular hyaluronan.
  • glycanic chains namely the collagens, the structural glycoproteins, the proteoglycans and the glycosaminoglycans (GAG chains), and in particular hyaluronan.
  • [ 3 H]glucosamine added to the culture medium of fibroblasts 1 ⁇ Ci/ml) permits radioactive labelling of all the newly synthesized glycoconjugates.
  • Skin fibroblasts are cultured on the basis of 1.5-3 x 10 5 cells per dish (nunc, 6 cm in diameter) in 5 ml of DMEM medium with 10% of foetal calf serum, 1% of penicillin/ streptomycin and 1% of fungizone, in a humid atmosphere containing 5% of CO2 and at 37°C. 24 hours later, the medium is replaced by a medium containing increasing doses of melibiose (0.1 , 1 or 5 ⁇ g/ml). The cells are cultured for 48 hours at 37°C with agitation. [ 3 H]Glucosamine ( 1 ⁇ Ci/ml), permitting radioactive labelling of all the newly synthesized glycoconjugates, is added.
  • the culture media are collected after two washes with 1 ml of OBS, 2 mM EDTA/PMSF, and the detached in the presence of 1 M urea.
  • the intra- and extracellular compartments are dialysed so as to remove non-incorporated radioactivity.
  • the radioactivity associated with [ 3 H]glucosamine is counted by liquid scintillation.
  • Control group Virtually all of the glucosamine incorporated is to be found in the extracellular compartment (90-95%). Only a small fraction is present in the in tra/ pericellular compartment.
  • [ 3 H]glucosamine incorporated is multiplied by a factor of 2.5 between passages 5 and 15. Hence a stimulation of the biosynthesis of the total glycoconjugates is observed during successive passages.
  • Intra/pericellular compartment ( Figure 5) .
  • the [ 3 H]glucosamine incorporated is multiplied by a factor of 4.2 between passages 5 and 15.
  • Extracellular compartment ( Figure 6) .
  • the [ 3 H]glucos- amine incorporated is multiplied by a factor of 3.5 between passages 5 and 15.
  • Intra/pericellular compartment ( Figure 5) .
  • the [ 3 H]glucosamine incorporated is multiplied by a factor of 1.3 at the early passage P5 and by a factor of 7.6 at the late passage P15 in the presence of melibiose at a dose of 1 ⁇ g/ml.
  • melibiose simultaneously stimulates the biosynthesis and inhibits the post-synthetic degradation of glycoconjugates, and of hyaluronan in particular, by skin fibroblasts. It is thus a cumulative double effect for increasing namely the amount of hyaluronan. This stimulation is more marked with "old" fibroblasts (late passages); very strong stimulations are obtained with very low concentrations of melibiose, of the order of 0.1 to 1 ⁇ g/ml.
  • Example 3 Anti-free-radical effect of melibiose
  • the degradation of hyaluronan by free radicals is determined by the fall in viscosity of a solution of Na hyaluronate at 37°C.
  • Example 4 Study on hairless rats of the anti-free-radical effect of melibiose or of lactose The defences against oxidative stress, reduced glutathione, glutathione peroxidase and also elastase, were measured after treatment with lactose and melibiose. A Solar Light type 1 148 lamp was used as UV source. The hairless rats were males of initial weight between 150 and 180 g.
  • the first group received melibiose in the form of a composition marketed by the company ROC (Anti-ageing melibiose), the second a lactose (L)/ melibiose (M) mixture containing 3% of each, and finally the third group received only the excipient.
  • the left side of the rats was not treated.
  • the treated surface area was of the order of 15 cm 2 .
  • the rats receive approximately 2 mg/cm 2 of each active principle.
  • the treatment lasted two weeks at the rate of 5 applications weekly.
  • the rats were anaesthetized and irradiated on both sides with the UV lamp at 6 spots at a dose of 3 MED.
  • the rats are anaesthetized again and the spots of irradiated skin are dissected, grouped in threes and weighed.
  • the mean fresh weight of the 3 spots was 266 ⁇ 25 mg.
  • the skins are then finely cut up and are ground in a Potter homogenizer with a buffer solution suitable for each assay, and the extracts are thereafter collected by centrifugation in Eppendorf tubes. The assays are performed on the extracts thereby obtained and the results are expressed with reference to the fresh weight of skin.
  • the method used for the assays is adapted from the method of Paglia and Valentine (D.E. Paglia and W.N. Valentine, J.
  • the substrate chosen is t-butyl hydroperoxide. It reacts according to the equation: ROOH + 2 GSH > GSSG + H 2 0 + ROH
  • GPX-catalysed reaction is supplied at the same time as NADPH and the glutathione reductase in order to permit recycling of the oxidized glutathione obtained after consumption of the GSH, according to the following reaction:
  • the oxidation of NADPH is monitored by spectro- photometry at 340 nm. This method permits the assay of total glutathione peroxidases.
  • the assay of glutathione peroxidase is carried out under the following conditions:
  • NADPH nicotinamide-adenine dinucleotide monophosphate reduced, in the form of the tetrasodium salt, Sigma t-Butyl hydroperoxide: Sigma C.H 10O2
  • Figure 8 shows the effect of the treatment on glutathione peroxidase, a selenium-containing enzyme, which plays an important part in protection against free radicals. It is apparent that the treatment with the active principles has greatly increased the glutathione peroxidase activity of the skin, confirming the anti- free-radical effect of lactose and melibiose.
  • Glutathione or ⁇ -glutamylcysteinylglycine tripeptide displays nucleophilic reducing properties which enable it to play an essential part in antioxidant protective systems. It is an important antioxidant since it is necessary for the activity of glutathione peroxidases.
  • Table 1 shows the increase in reduced glutathione (GSH) content of the skin irradiated with UV and treated as above:
  • No. 1 prep. RoC; No. 2: L + M; No. 3: control
  • EDTA is a selective inhibitor of metalloendopeptidases. When its effect on the results of the assays is considered, it is observed in the irradiated skins that, initially (2.5 and 4.5 hours of incubation), only a small part of the elastase activity is inhibited, indicating that virtually all of the measured activity relates to PMN (polymorphonuclear leukocyte) elastase. On the unirradiated side, a relatively high activity is also observed, attributable to the effect of cytokines released at the sites of irradiation and acting at a distance. At these points, the addition of EDTA increases the measured activity by 55%, which may be attributed to an activation by EDTA, by complexing of trace metals, of the PMN serine proteases which are partially inhibited by these metals.
  • Figure 9 gives the inhibition of elastase activities measured in the extracts of skin irradiated and treated with melibiose (RoC "Anti-ageing melibiose”): group No. 1 ; or with a mixture of 3% lactose/ melibiose in an excipient: group No. 2; or with the excipient alone: group No. 3.
  • the preparations containing lactose and/or melibiose produced a protection of the order of 30% against the increase in elastase activity induced in the skin by UV irradiation.

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EP98914000A 1997-05-02 1998-04-30 Use of oligosaccharides for the treatment of connective tissues Withdrawn EP0979065A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
FR9705464A FR2762783B1 (fr) 1997-05-02 1997-05-02 Utilisation d'oligosaccharides pour le traitement du tissu conjonctif et methode de traitement cosmetique mettant en oeuvre ces oligosaccharides
FR9705464 1997-05-02
PCT/IB1998/000657 WO1998050013A1 (en) 1997-05-02 1998-04-30 Use of oligosaccharides for the treatment of connective tissues

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EP0979065A1 true EP0979065A1 (en) 2000-02-16

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EP98914000A Withdrawn EP0979065A1 (en) 1997-05-02 1998-04-30 Use of oligosaccharides for the treatment of connective tissues

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EP (1) EP0979065A1 (pt)
JP (1) JP2001524122A (pt)
KR (1) KR20010012159A (pt)
AR (1) AR012642A1 (pt)
AU (1) AU6850098A (pt)
BR (1) BR9809589A (pt)
CA (1) CA2288773A1 (pt)
CO (1) CO4940384A1 (pt)
FR (1) FR2762783B1 (pt)
PL (1) PL336592A1 (pt)
WO (1) WO1998050013A1 (pt)

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FR2795956B1 (fr) * 1999-07-06 2006-07-14 Inst Evaluation Dermatophysiqu Composition cosmetique pour ameliorer l'elasticite de la peau et lutter contre son vieillissement
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
KR100839648B1 (ko) * 2008-03-04 2008-06-19 씨에이치디메딕스 주식회사 모근의 진피층 보강과 보습을 통한 탈모방지 조성물
GB2500585A (en) * 2012-03-23 2013-10-02 Univ Manchester Use of oligosaccharides to reduce skin pigmentation
WO2024150915A1 (ko) * 2023-01-11 2024-07-18 주식회사 풀바이오스 미세먼지로 인한 피부 손상 보호 및 탈모 방지용 조성물 및 그 제조방법
FR3152121A1 (fr) 2023-08-16 2025-02-21 Sederma Exopolysaccharide et oligosaccharides notamment pour la cosmétique

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FR2709061B1 (fr) * 1993-08-17 1996-07-19 Ladislas Robert Utilisation d'oligosaccharides dans la prévention et le traitement du vieillissement des tissus.
FR2730409B1 (fr) * 1995-02-15 1997-05-09 Dior Christian Parfums Utilisation des galactolipides, en particulier galactosylglycerides, et des extraits d'origine naturelle contenant ces produits, dans les domaines cosmetiques, pharmaceutique et notamment dermatologique
FR2739556B1 (fr) * 1995-10-04 1998-01-09 Oreal Utilisation de carbohydrates pour favoriser la desquamation de la peau

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JP2001524122A (ja) 2001-11-27
BR9809589A (pt) 2000-07-04
CA2288773A1 (en) 1998-11-12
FR2762783A1 (fr) 1998-11-06
CO4940384A1 (es) 2000-07-24
FR2762783B1 (fr) 2002-09-13
AU6850098A (en) 1998-11-27
KR20010012159A (ko) 2001-02-15
PL336592A1 (en) 2000-07-03
AR012642A1 (es) 2000-11-08

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