WO2009031099A2 - Cosmetic use of microorganisms - Google Patents

Cosmetic use of microorganisms Download PDF

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Publication number
WO2009031099A2
WO2009031099A2 PCT/IB2008/053546 IB2008053546W WO2009031099A2 WO 2009031099 A2 WO2009031099 A2 WO 2009031099A2 IB 2008053546 W IB2008053546 W IB 2008053546W WO 2009031099 A2 WO2009031099 A2 WO 2009031099A2
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WO
WIPO (PCT)
Prior art keywords
lactobacillus
microorganism
skin
treatment
fraction
Prior art date
Application number
PCT/IB2008/053546
Other languages
French (fr)
Other versions
WO2009031099A3 (en
Inventor
Isabelle Castiel
Audrey Gueniche
Original Assignee
L'oreal
Nestec Sa
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 L'oreal, Nestec Sa filed Critical L'oreal
Publication of WO2009031099A2 publication Critical patent/WO2009031099A2/en
Publication of WO2009031099A3 publication Critical patent/WO2009031099A3/en

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/99Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from microorganisms other than algae or fungi, e.g. protozoa or bacteria
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9728Fungi, e.g. yeasts
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/005Preparations for sensitive skin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/74Biological properties of particular ingredients
    • A61K2800/75Anti-irritant

Definitions

  • the present invention relates to the field of topical products, food supplements or functional foods intended for skincare.
  • the invention more particularly relates to the cosmetic use of at least one microorganism, especially a probiotic microorganism, or a fraction thereof, as an agent for preventing the appearance and/or for treating the manifestation of sensations of discomfort and/or of cutaneous signs associated with a surface skin treatment, especially of aggressive nature, or with an invasive treatment for aesthetic purposes.
  • Non-limiting illustrations of such treatments that may especially be mentioned include chemical peeling treatments, laser treatments, filling injections, or aesthetic surgery operations.
  • these undesirable side reactions may occur in two aspects, namely in the form of sensations of discomfort experienced on the skin and/or by the appearance of cutaneous signs, defined as follows.
  • the expression "sensation of discomfort” covers any unpleasant sensation, or even pain, which is undesirable to the user.
  • the cutaneous signs may be a matter of bleaching followed by vesiculation, dyschromia, desquamation, redness, dry patches, inflammatory erythema, oedema and/or pimples.
  • the object of the present invention is, precisely, to satisfy this need.
  • compositions for treating sensitive skin using, as active agent, a combination of a Lactobacillus paracasei or casei microorganism and of a Bifidobacterium longum or Bifidobacterium lactis microorganism.
  • FR 2 872 047 this document describes a combination of a microorganism with a divalent mineral cation.
  • FR 2 889 057 discloses a topical composition comprising a microorganism in combination with a polyunsaturated fatty acid and/or a polyunsaturated fatty acid ester, which is useful for treating sensitive skin.
  • WO 02/28402 describes, for its part, the use of probiotic microorganisms for regulating cutaneous hypersensitivity reactions, for instance inflammatory and allergic reactions.
  • WO 03/070 260 concerns the use of probiotic microorganisms for skin photoprotection purposes.
  • the inventors have found, unexpectedly, that the use of an effective amount of at least one microorganism, especially a probiotic microorganism, or a fraction thereof, proves to be most particularly effective for preventing the appearance and/or for treating the manifestation of sensations of discomfort and/or of cutaneous signs, or even an impairment in the cutaneous barrier function, associated with a surface skin treatment or an invasive treatment for aesthetic purposes.
  • the inventors have been able to demonstrate that the use under consideration according to the invention makes it possible especially to restore the homeostasis of a skin tissue, or even to reconstitute the barrier function, if necessary.
  • the present invention relates to the cosmetic use of an effective amount of at least one microorganism, especially a probiotic microorganism, or a fraction thereof, as an agent for preventing the appearance of and/or for treating skin disorders especially of the type such as sensations of discomfort and/or cutaneous signs associated with a surface skin treatment or an invasive treatment for aesthetic purposes.
  • the sensation of discomfort may be a dysaesthesic sensation, chosen especially from stinging, tingling, itching or pruritus, burning, a sensation of heating, a sensation of dryness, erythema and/or tautness.
  • the cutaneous sign may be chosen from bleaching followed by vesiculation, dyschromia, desquamation, redness, dry patches, inflammatory erythema, oedema and/or pimples.
  • the sensations of discomfort and/or the cutaneous signs may be associated with, and, for example, be consecutive to, a surface skin treatment for aesthetic purposes, especially as described hereinbelow.
  • the sensations of discomfort and/or cutaneous signs may be associated with, and, for example, be consecutive to, an invasive treatment for aesthetic purposes, especially as described hereinbelow.
  • the microorganism, especially the probiotic microorganism, or a fraction thereof, under consideration according to the invention may be used as an agent for maintaining and/or restoring the biomechanical properties of the skin, especially in the case of an individual destined to undergo or who has already undergone at least one surface skin treatment and/or at least one invasive treatment for aesthetic purposes.
  • a treatment with a microorganism in accordance with the invention promotes the recovery and maintenance of the cutaneous barrier function.
  • the invention also relates to the cosmetic use of an effective amount of at least one microorganism, especially a probiotic microorganism, or a fraction thereof, for promoting the recovery and/or maintenance of a cutaneous barrier function that is impaired or liable to be impaired by a surface skin treatment or an invasive treatment for aesthetic purposes.
  • the invention also relates to the use of an effective amount of at least one microorganism, especially a probiotic microorganism, or a fraction thereof, for the preparation of a composition, especially a cosmetic and/or therapeutic composition, for preventing the appearance of and/or for treating skin disorders especially of the type such as sensations of discomfort and/or cutaneous signs associated with a surface skin treatment or an invasive treatment for aesthetic purposes.
  • the invention is also directed towards the use of an effective amount of at least one microorganism, especially a probiotic microorganism, or a fraction thereof, for the preparation of a composition for promoting the recovery and/or maintenance of a cutaneous barrier function that is impaired or liable to be impaired by a surface skin treatment or an invasive treatment for aesthetic purposes.
  • the present invention also relates to a cosmetic treatment process comprising at least one step of administering to an individual an effective amount of at least one microorganism, especially a probiotic microorganism, or a fraction thereof, the said process being intended to be performed before or after the application to the said individual of at least one surface skin treatment and/or at least one invasive treatment for aesthetic purposes.
  • it may be a cosmetic process for preparing the skin of an individual destined to undergo at least one surface skin treatment and/or at least one invasive treatment for aesthetic purposes, comprising at least one step of administering to the said individual an effective amount of at least one microorganism, especially a probiotic microorganism, or a fraction thereof.
  • the administration under consideration according to the invention may be useful for preventing the appearance of sensations of discomfort and/or cutaneous signs associated with the said treatment for aesthetic purposes.
  • it may be a cosmetic process for smoothing the skin of an individual who has undergone at least one surface skin treatment and/or at least one invasive treatment for aesthetic purposes, comprising at least one step of administering to the said individual an effective amount of at least one microorganism, especially a probiotic microorganism, or a fraction thereof.
  • the process according to the invention may especially be applied to an individual with damaged skin, especially a cutaneous barrier function that has been impaired as a result of the said treatment for aesthetic purposes.
  • the term "preventing” means reducing the risk of occurrence of the manifestation under consideration.
  • skin means any cutaneous surface of the body, including the skin and broadened to the scalp and to the mucous and semi-mucous membranes.
  • the term "effective amount” means an amount that is sufficient to obtain the expected effect.
  • microorganism especially the probiotic microorganism, or a fraction thereof, under consideration according to the invention may be formulated in cosmetic or dermatological compositions.
  • the use or the process according to the invention may comprise the administration of at least one microorganism, especially a probiotic microorganism, or a fraction thereof, or of compositions comprising the same, topically, orally or parenterally, preferably topically or orally.
  • topically means an administration of the microorganism, especially the probiotic microorganism, or a fraction thereof, or of compositions comprising the same, by application to the skin, as defined above.
  • the use or the process according to the invention may comprise the administration of at least one microorganism, especially a probiotic microorganism, or a fraction thereof, or of compositions comprising the same, aerially or subcutaneously.
  • the subcutaneous administration may especially be performed using a syringe.
  • treatment for aesthetic purposes means any treatment for remedying an imperfection deemed as being unsightly, and more generally any treatment for beautifying, i.e. for enhancing the appearance of, the individual undergoing such a treatment.
  • the treatments for aesthetic purposes under consideration according to the invention may more particularly be surface skin treatments or invasive treatments for aesthetic purposes.
  • surface skin treatment for aesthetic purposes means treatments liable to have an aggressive nature with regard to the epidermis and especially liable to cause skin irritation. They may especially be chemical peeling treatments and laser treatments.
  • peeling conventionally denotes a controlled action of irritation of the surface of the skin with a chemical substance or via a physical process.
  • An operation of peeling type may consist, for example, in applying to the skin a chemical substance for the purpose of bringing about limited and controlled destruction of the epidermis and of the upper layers of the dermis, in order to improve certain disorders of the cutaneous appearance.
  • a surface peeling treatment targets the epidermis and is based on a surface attack of the skin. It affects the epidermis either partially or entirely. It may concern only the stratum corneum (SC) or may go as far as the stratum granulosum or the basal layer depending on the type of agent used, its concentration, the number of applications and the prior degreasing of the skin. This type of peeling treatment is of little efficacy when it is applied only once.
  • SC stratum corneum
  • This type of peeling treatment is of little efficacy when it is applied only once.
  • the AHAs used for surface peeling treatments are keratolytic but do not modify the keratin of corneocytes. They impair the membrane of the corneocytes, giving it a serrated contour, they cause ruptures in the lipid envelope of the corneocytes and target the corneodesmosomes and the desmo somes: they thus cause desquamation in large plaques.
  • they require an acidic pH to have optimum activity. They are also used at higher doses in peeling treatments. Glycolic acid or hydroxyacetic acid is the most well known of these agents.
  • GIy co lie acid is the smallest member of the AHAs (chain containing two carbon atoms), and its size thus enables it to penetrate easily into the horny layer.
  • citric acid citrus fruit
  • malic acid green apple
  • tartaric acid grain
  • lactic acid milk, red berries
  • glycolic acid is present in nature.
  • glycolic acid The properties of glycolic acid are associated with the activation of desquamation. It thus promotes exfoliation of the dead surface cells, which takes place less efficiently with age, in order to restore the qualities of the skin surface (clarity, luminosity, uniformity of complexion, softness, smoothness of the skin relief and action on skin imperfections). Furthermore, it helps towards combating the hyperkeratinization of skin imperfections and thus contributes towards reducing them.
  • the first ablative lasers produced with pulsed or scanned CO 2 lasers, have the immediate effect of vaporizing (or ablating) the epidermis and often the upper part of the dermis.
  • a strip of the subjacent dermis is generally also the site of a thermal lesion with denaturation and contraction of collagen.
  • re-epithelization takes place from the hair follicles and other appendages in addition to an upper dermal strip ("collagen remodelling").
  • collagen remodelling The latest generation of lasers uses a system for transforming the laser beam into a multitude of spaced-out beams in order to produce on the skin spaced-out impacts, thus maintaining areas of unimpaired healthy skin between the affected areas.
  • laser treatment means any treatment for aesthetic purposes using a laser, including the physical peeling treatments described previously.
  • laser treatments examples include laser depilation; laser treatment of angiomas; laser treatment of redness, especially of erythrosis or rosacea; laser treatment of lentigo, especially actinic lentigo; laser treatment of tattoos; or laser treatment of wrinkles.
  • filling injection is intended to denote any injection of compounds intended to afford an aesthetic effect.
  • the injection methods may be of retrograde tracing or multi-puncture type. It may especially concern an injection of collagen, an injection of hyaluronic acid or an injection of type A botulinum toxin (sold under the name Botox®).
  • These compounds may be injected into the skin, and thus create volume, giving an appearance of vitality and good health.
  • lift generally denotes all the operations intended to correct collapse of the skin, for example collapse of the cheekbones and of the hollows in the middle of the cheeks.
  • a lift may thus also be performed, where appropriate, via an aesthetic surgery operation.
  • the term "aesthetic surgery” is intended to denote surgery directed especially towards correcting congenital unsightly physical features (nose, ears or chin) or unsightly physical features acquired at puberty (mammary hypotrophy, or localized excess fat), as a result of pregnancy (deformation of the abdominal wall) or as a result of ageing (face, eyebrows, neck or breasts).
  • Aesthetic surgery operations that may thus also be mentioned include, in a non- limiting manner, blepharoplasty, abdominal plasty (or abdominoplasty), rhinoplasty, mammary plasty, liposuction and lipostructure.
  • Microorganisms especially probiotic microorganisms
  • microorganisms that are suitable for use in the invention are microorganisms that may be administered without risk to man or animals.
  • at least one microorganism of "probiotic” type is used in the present invention.
  • probiotic microorganism means a live microorganism which, when consumed in adequate amount, has a positive effect on the health of its host ("Joint FAO/WHO Expert Consultation on Evaluation of Health and Nutritional Properties of Probiotic in Food Including Powder Milk with Live Lactic Acid Bacteria, 6 October 2001”), and which may in particular improve the intestinal microbial equilibrium.
  • this microorganism is used in an isolated form, i.e. not mixed with one or more compound(s) liable to be associated therewith in its medium of origin.
  • the term "fraction” more particularly denotes a fragment of the said microorganism that has efficacy in treating dry skin by analogy with the said whole microorganism.
  • the microorganisms that are suitable for use in the invention may be chosen especially from ascomycetes such as Saccharomyces, Yarrowia, Kluyveromyces, Torulaspora, Schizosaccharomyces pombe, Debaromyces, Candida, Pichia, Aspergillus and Penicillium, bacteria of the genera Bifidobacterium, Bacteroides, Fusobacterium, Melissococcus, Propionibacterium, Enter ococcus, Lactococcus, Staphylococcus, P eptostrepococcus , Bacillus, Pediococcus, Micrococcus, Leuconostoc, Weissella, Aerococcus, Oenococcus and Lactobacillus, and mixtures thereof.
  • lactic acid bacteria which produce lactic acid by fermentation of sugar. According to their morphology, they are divided into two groups: • Lactobacillus species: Lactobacillus acidophilus, amylovorus, casei, rhamnosus, brevis, crispatus, delbrueckii (subsp bulgaricus, lactis), fermentum, helveticus, gallinarum, gasseri johnsonii, paracasei, plantarum, reuteri, salivarius, alimentarius, curvatus, casei subsp. casei, sake
  • Pediococcus acidilactici Sporolactobacillus inulinus, Streptococcus salvarius subsp. Thermophilus, Streptococcus thermophilus,
  • Staphylococccus carnosus Staphylococcus xylosus bifidobacteria or Bifidobacterium species: Bifidobacterium adolescentis, animalis, bifidum, breve, lactis, longum, infantis, pseudocatenulatum, yeasts: Saccharomyces (cerevisiae or boulardii), - other sporulating bacteria: Bacillus (cereus var toyo or subtilis), Bacillus coagulans, Bacillus licheniformis, Escherichia coli strain nissle, Propionibacterium freudenreichii, and mixtures thereof.
  • Lactic acid bacteria and bifidobacteria are the probiotics most commonly used.
  • Specific examples of probiotic microorganisms are Bifidobacterium adolescentis,
  • Bifidobacterium animalis Bifidobacterium bifidum, Bifidobacterium breve,
  • Lactobacillus casei (Shirota), Lactobacillus rhamnosus (strain GGA Lactobacillus brevis, Lactobacillus crispatus, Lactobacillus delbrueckii (subsp bulgaricus, lactis), Lactobacillus fermentum, Lactobacillus helveticus, Lactobacillus gallinarum, Lactobacillus gasseri,
  • Lactobacillus johnsonii (CNCM 1-1225), Lactobacillus paracasei, Lactobacillus plantarum, Lactobacillus reuteri, Lactobacillus salivarius, Lactobacillus alimentarius,
  • Lactobacillus curvatus Lactobacillus casei subsp. casei, Lactobacillus sake, Lactococcus lactis, Enterococcus (faecalis, faecium), Lactococcus lactis (subspp lactis or cremoris),
  • the probiotic microorganism may be chosen from: Lactobacillus acidophilus, Lactobacillus alimentarius, Lactobacillus curvatus, Lactobacillus delbruckii (subsp. bulgaricus lactis), Lactobacillus gasseri, Lactobacillus johnsonii, Lactobacillus reuteri, Lactobacillus rhamnosus (strain GG), Lactobacillus sake, Lactococcus lactis, Streptococcus thermophilus, Staphylococccus carnosus and Staphylococcus xylosus, and mixtures thereof.
  • These microorganisms may be formulated in the form of powders, i.e. in a dry form, or in the form of suspensions or solutions.
  • probiotic microorganisms derived from the group of lactic acid bacteria especially such as Lactobacillus and/or Bifidobacterium.
  • these lactic acid bacteria mention may be made more particularly of Lactobacillus johnsonii, Lactobacillus reuteri, Lactobacillus rhamnosus, Lactobacillus paracasei, Lactobacillus casei or Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium animalis, Bifidobacterium lactis, Bifidobacterium infantis, Bifidobacterium adolescentis or Bifidobacterium pseudocatenulatum and mixtures thereof, and preferably Lactobacillus johnsonii, Lactobacillus reuteri, Lactobacillus rhamnosus and Lactobacillus paracasei, and mixtures thereof.
  • the species that are most particularly suitable for use are Lactobacillus johnsonii, Lactobacillus paracasei, Bifidobacterium adolescentis, Bifidobacterium longum and Bifidobacterium lactis NCC 2818, which were deposited, respectively, according to the treaty of Budapest, at the Institut Pasteur (28, rue du Dondel Roux, F-75024 Paris cedex 15) on 30/06/92, 12/01/99, 15/04/99, 15/04/99 and 07/06/05 under the following designations CNCM 1-1225, CNCM 1-2116, CNCM 1-2168 and CNCM 1-2170 and CNCM 1-3446, and the genus Bifidobacterium longum (BB 536), and mixtures thereof.
  • the probiotic microorganism is of the genus Lactobacillus species, in particular the species Lactobacillus johnsonii and more particularly of the species Lactobacillus paracasei, or a fraction thereof.
  • the probiotic microorganism is the strain of Lactobacillus paracasei deposited, according to the treaty of Budapest, at the Institut Pasteur (28, rue du Dondel Roux, F-75024 Paris cedex 15) on 12/01/99 under the designation CNCM 1-2116.
  • a composition according to the invention may comprise at least two different microorganisms, especially probiotic microorganisms, and/or fractions thereof.
  • the microorganism(s) may be included in the composition according to the invention in a live, semi-active or inactivated, dead form.
  • compositions according to the invention may comprise from
  • microorganism(s), especially probiotic microorganism(s), relative to the total weight of the composition 0.00001% to 20% by weight, in particular from 0.001% to 20% by weight and more particularly from 0.01% to 10% by weight of microorganism(s), especially probiotic microorganism(s), relative to the total weight of the composition.
  • microorganisms in inactivated or even dead form, and more particularly in the form of a lysate.
  • Such a lysate may be obtained from the cell lysis of the microorganism concerned, according to a conventional method.
  • the probiotic microorganism(s) in the form of a disintegrated lysate in suspension may be formulated in a suitable support in a proportion of less than 20% by weight, in particular in a proportion of from 0.0001% to 20% by weight and more particularly in a proportion of from 0.01% to 10% by weight relative to the total weight of the said support.
  • the microorganisms and/or the fractions thereof may be formulated in a suitable support in an amount equivalent to at least 10 3 cfu/g, in particular at doses ranging from 10 5 to 10 15 cfu/g and more particularly from 10 7 to 10 12 cfu/g of support.
  • compositions according to the invention generally comprise from 10 3 to 10 12 cfu, in particular from 10 5 to 10 10 cfu and more particularly from 10 7 to 10 9 cfu of live microorganisms, especially probiotic microorganisms, per gram of support.
  • the compositions according to the invention may be in any galenical form normally available for the selected mode of administration.
  • the support may be of diverse nature according to the type of composition under consideration.
  • compositions for external topical administration they may be aqueous, aqueous-alcoholic or oily solutions, dispersions of the solution type or dispersions of the lotion or serum type, emulsions of liquid or semi- liquid consistency of the milk type, suspensions or emulsions of the cream type, aqueous or anhydrous gels, microemulsions, microcapsules, microparticles, or vesicular dispersions of ionic and/or nonionic type.
  • compositions are prepared according to the usual methods.
  • galenical forms dedicated to topical administration may also contain adjuvants that are common in cosmetics, pharmaceutics and/or dermatology, such as hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic active agents, preserving agents, antioxidants, solvents, fragrances, fillers, screening agents, bactericides, odour absorbers and dyestuffs.
  • adjuvants that are common in cosmetics, pharmaceutics and/or dermatology, such as hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic active agents, preserving agents, antioxidants, solvents, fragrances, fillers, screening agents, bactericides, odour absorbers and dyestuffs.
  • the amounts of these various adjuvants are those conventionally used in the field under consideration, for example from 0.01% to 20% of the total weight of the composition. Depending on their nature, these adjuvants may be introduced into the fatty phase and/or into the a
  • mineral oils for instance hydrogenated polyisobutene and liquid petroleum jelly
  • plant oils for instance a liquid fraction of shea butter, sunflower oil and apricot kernel oil
  • animal oils for instance perhydrosqualene
  • synthetic oils especially purcellin oil, isopropyl myristate and ethylhexyl palmitate
  • unsaturated fatty acids and fluoro oils for instance perfluoropolyethers.
  • fatty alcohols fatty acids, for instance stearic acid and, for example, waxes, especially paraffin wax, carnauba wax and beeswax.
  • Silicone compounds may also be used, for instance silicone oils, for example cyclomethicone and dimethicone, silicone waxes, silicone resins and silicone gums.
  • emulsif ⁇ ers that may be used in the invention, examples that may be mentioned include glyceryl stearate, polysorbate 60, the mixture of cetylstearyl alcohol/cetylstearyl alcohol oxyethylenated with 33 mol of ethylene oxide, sold under the name Sinnowax AO® by the company Henkel, the mixture of PEG-6/PEG-32/glycol stearate sold under the name Tefose® 63 by the company Gattefosse, PPG-3 myristyl ether, silicone emulsif ⁇ ers such as cetyldimethicone copolyol and sorbitan monostearate or tristearate, PEG-40 stearate, and oxyethylenated (20 EO) sorbitan monostearate.
  • composition of the invention may also advantageously contain a spring and/or mineral water, chosen especially from Vittel water, waters from the Vichy Basin, and Ia Roche Posay water.
  • the ingestible support may be of diverse nature according to the type of composition under consideration.
  • oral supplements in dry form and oral supplements in liquid form are thus especially suitable for use as pharmaceutical or food supports. They may be, for example, food supplements, the formulation of which may be performed via the usual processes for especially producing coated tablets, gel capsules, gels, emulsions, tablets, wafer capsules and hydrogels allowing controlled release.
  • the microorganism according to the invention may be incorporated into any other form of food supplement or enriched food, for example food bars or compacted or non-compacted powders.
  • the powders may be diluted in water, soda, dairy products or soybean derivatives, or may be incorporated into food bars.
  • the microorganism especially the probiotic microorganism, or a fraction thereof, may moreover be formulated with the usual excipients and components for such oral compositions or food supplements, i.e. especially fatty and/or aqueous components, humectants, thickeners, preserving agents, texture agents, taste agents and/or coating agents, antioxidants, preserving agents and dyes that are common in the food sector.
  • excipients and components for such oral compositions or food supplements i.e. especially fatty and/or aqueous components, humectants, thickeners, preserving agents, texture agents, taste agents and/or coating agents, antioxidants, preserving agents and dyes that are common in the food sector.
  • the formulating agents and excipients for oral compositions, and especially for food supplements, are known in this field and will not be the subject of a detailed description herein.
  • Milk, yoghurt, cheese, fermented milks, milk-based fermented products, ice creams, cereal-based products or fermented cereal-based products, milk-based powders, infant and baby formulae, food products of confectionery, chocolate or cereal type, animal feed in particular for pets, tablets, gel capsules or lozenges, liquid bacterial suspensions, oral supplements in dry form and oral supplements in liquid form are especially suitable as pharmaceutical or food supports.
  • the effective amount of the microorganism, especially the probiotic microorganism, or a fraction thereof may also be advantageously combined with at least one other active agent.
  • active agents that may be used, mention may be made of vitamin A, B3, B5, B6, B8, C, D, E or PP, curcuminoids, carotenoids, polyphenol compounds and mineral compounds, sugars, amino acids, sulfur-containing amino acids, 3 and 6 polyunsaturated fatty acids, taurine and phytosterols.
  • an antioxidant complex comprising vitamins C and E, and at least one carotenoid, especially a carotenoid chosen from ⁇ -carotene, lycopene, astaxanthin, zeaxanthin and lutein, flavonoids such as catechins, proanthocyanidins, anthocyanins, ubiquinones, coffee extracts containing polyphenols and/or diterpenes, extracts of chicory, extracts of ginkgo biloba, extracts of grape rich in proanthocyanidins, extracts of pimento, extracts of soybean, other sources of flavonoids having antioxidant properties, fatty acids, prebiotic agents, taurine, resveratrol, selenium- containing amino acids, and glutathione precursors.
  • a carotenoid chosen from ⁇ -carotene, lycopene, astaxanthin, zeaxanthin and lutein, flavonoids such as catechins, proanthocyanidins, anthocyan
  • catechins and PCOs are preferably chosen.
  • Proteins or protein hydro lysates, amino acids, polyols, especially of C 2 to C 10 , for instance glycerol, sorbitol, butylene glycol and polyethylene glycol, urea, allantoin, sugars and sugar derivatives, water-soluble vitamins, starch, and bacterial or plant extracts such as those of Aloe vera, may be used more particularly as hydrophilic active agents in the topical galenical forms.
  • retinol and derivatives thereof
  • tocopherol vitamin E
  • ceramides essential oils and unsaponif ⁇ able materials (tocotrienol, sesamine, gamma-oryzanol, phytosterols, squalenes, waxes and terpenes) may be used.
  • any ingredient commonly used and/or permitted, especially active agents for preventing and/or treating skin complaints, may also be considered.
  • Illustrations that may be mentioned include vitamins, minerals, essential lipids, trace elements, polyphenols, flavonoids, phyto-oestrogens, antioxidants such as lipoic acid and coenzyme QlO, carotenoids, prebiotic agents, proteins and amino acids, monosaccharides and polysaccharides, amino sugars, phytosterols and triterpenic alcohols of plant origin. They are, in particular, vitamins A, C, D, E and PP and group B vitamins.
  • the carotenoids ⁇ -carotene, lycopene, lutein, zeaxanthin and astaxanthin are preferably chosen.
  • the minerals and trace elements particularly used are zinc, calcium, magnesium, copper, iron, iodine, manganese, selenium and chromium (III).
  • polyphenols from grape, from tea, from olive, from cocoa, from coffee, from apple, from blueberry, from elderberry, from strawberry, from cranberry and from onion are also selected in particular.
  • isoflavones in free or glycosylated form are selected, such as genistein, daidzein, glycitein or lignans, in particular those from flax and from Schizandra chinensis.
  • the amino acids or the peptides and proteins containing them such as taurine, threonine, cysteine, tryptophan or methionine.
  • the lipids preferably belong to the group of oils containing monounsaturated and polyunsaturated fatty acids such as oleic acid, linoleic acid, ⁇ -linolenic acid, ⁇ - linolenic acid, stearidonic acid, long-chain fish omega-3 fatty acids such as EPA and DHA, and conjugated fatty acids derived from plants or animals, such as CLAs (conjugated linoleic acid).
  • the microorganism, especially the probiotic microorganism, or a fraction thereof when intended for oral administration, it may also be combined with at least one nutritional active agent chosen from lycopene, vitamin C, vitamin E and polyphenol compounds.
  • the microorganism, especially the probiotic microorganism, or a fraction thereof, or a combination according to the invention may also be combined with other nutritional active agents chosen from: anti-ageing nutritional active agents, such as food antioxidants, nutrients with free-radical-scavenging properties and cofactors of antioxidant endogenous enzymes, vitamins A, C and E, carotenoids, xanthophylls, isoflavones, certain minerals such as zinc, copper, magnesium or selenium, lipoic acid, coenzyme QlO, superoxide dismutase (SOD) or taurine.
  • anti-ageing nutritional active agents such as food antioxidants, nutrients with free-radical-scavenging properties and cofactors of antioxidant endogenous enzymes
  • vitamins A, C and E
  • anti-ageing active agents mention may be made especially of the unsaponif ⁇ able fractions extracted from lipids of plant origin, Aloe vera, native or hydro lysed marine collagen, and plant or marine oils rich in omega-3 and omega-6 fatty acids (including ⁇ -linolenic acid), photoprotective nutritional active agents such as: antioxidants and free- radical scavengers, vitamins A, C and E, carotenoids, xanthophylls, certain minerals such as zinc, copper, magnesium or selenium, coenzyme QlO and superoxide dismutase (SOD), nutritional ingredients with moisturizing or immunomodulating properties, such as an extract of Polypodium leucotomos, and plant or marine oils rich in omega-3 and omega-6 fatty acids, including ⁇ -linolenic acid, nutritional active agents that are active on the clinical signs of the menopause (for example hot flushes, etc.), such as isoflavones, lignans, DHEA, extracts of y
  • the cosmetic treatment process of the invention may be performed especially by orally and/or topically administering at least an effective amount of at least one microorganism, especially a probiotic microorganism, or a fraction thereof.
  • the topical administration consists of the external application to the skin of cosmetic and/or dermato logical compositions according to the usual technique for using these compositions.
  • the cosmetic process according to the invention may be performed by topical administration, for example daily, of cosmetic and/or dermato logical compositions, which may be formulated, for example, in the form of gels, lotions or emulsions.
  • the oral administration consists in ingesting in one or more intakes an oral composition as defined above.
  • the cosmetic process comprises at least one step of oral administration of an effective amount of at least one microorganism, especially a probiotic microorganism, or a fraction thereof, and at least one step of topical administration of an effective amount of at least one microorganism, especially a probiotic microorganism, or a fraction thereof.
  • the process according to the invention may comprise a single administration.
  • the administration is repeated, for example two to three times daily for one day or more and generally for an extended period of at least 4 weeks, or even 4 to 15 weeks, with, where appropriate, one or more periods of stoppage.
  • the percentages are weight percentages and the ranges of values written in the form "between ... and " include the stated lower and upper limits.
  • the ingredients are mixed, before being formed, in the order and under conditions that may be readily determined by those skilled in the art.
  • a dose of from 200 to 400 ml per day may be taken.
  • One to three of these capsules may be taken per day.
  • a vitamin complex comprising 60 mg of vitamin C, 100 ⁇ g of vitamin E and 6 mg of ⁇ -carotene is added to the formulation of Example 2.
  • Example 4 A vitamin complex comprising 60 mg of vitamin C, 100 ⁇ g of vitamin E and 6 mg of ⁇ -carotene is added to the formulation of Example 2.
  • a vitamin complex comprising 100 mg of vitamin C, 100 ⁇ g of vitamin E and mg of lycopene per capsule is added to the formulation of Example 2.
  • Example 5 Body lotion in spray form
  • Lactobacillus paracasei (CNCM 1-2116) 5.00
  • Lactobacillus johnsonii (CNCM 1-1225) 5.00
  • Lactobacillus paracasei (CNCM 1-2116) 10 10 cfu Antioxidant O .05 Vitamin C 2 .50
  • Antioxidant O .05 Isopropanol 40 .00
  • Example 8 Effect of a food supplement comprising a microorganism in accordance with the invention on cutaneous reactivity and reconstitution of the barrier function
  • strain Lactobacillus paracasei CNCM 1-2116 was tested alone, in a double-blind randomized study.
  • product B a second group of 32 women, to whom was administered Lactobacillus paracasei CNCM 1-2116 alone (referred to hereinbelow as "product B").
  • the cutaneous reactivity of the two groups of women was measured according to the following test with capsaicin, in which the concentration of capsaicin perceived makes it possible to assess the reactivity of the skin.
  • capsaicin solutions were applied to the nasolabial folds, from the nostril wall to the corner of the mouth, by wiping with a single-use cotton-tipped applicator (Societe Industrielle du Bois) impregnated with an average volume of 0.2 ml of solution and depositing an average volume of 0.02 ml of solution (volumes measured by differential weighing).
  • a single-use cotton-tipped applicator Societe Industrielle du Bois impregnated with an average volume of 0.2 ml of solution and depositing an average volume of 0.02 ml of solution (volumes measured by differential weighing).
  • 1st step the nasolabial folds were cleansed/freed of makeup using a gauze impregnated with an aqueous-alcoholic solution containing 10% ethano 1.
  • 3rd step 2 minutes after step 2, solution Cl of capsaicin and the vehicle are applied simultaneously, under single-blind conditions, to the nasolabial folds, in accordance with a randomization list that sets the application sides.
  • the detected capsaicin concentration is recorded (the test stopping at that concentration).
  • the table below presents, for each group of women and for each visit, the mean and the standard deviation of the values of the capsaicin solution detected on Dl, D29, D43 and D57.
  • the reactivity threshold of the volunteers varies randomly according to the evaluation day (decrease on D29, increase on D43 and then slight decrease again on D57).
  • the volunteers treated with product B show a gradual uniform decrease in their reactivity threshold, resulting at all times in decreases that are significantly different relative to their reactivity threshold on Dl .
  • TWL transepidermal water loss
  • This measurement consists of the repeated application of a strip of dermatological adhesive tape to the skin of the inner face of one of the volunteer's forearms, the operation being recommenced as many times as necessary (repeated tape strippings).
  • TWL transepidermal water loss
  • a threshold value of -12 corresponds to the TWL value (as an absolute value) that is necessary to return to the TWL value before stripping.
  • the healthy volunteers have a TWL value of between 5.1 ⁇ 2.6 and 6.5 ⁇ 2.6, and the performed strippings lead to an increase of their TWL value to between 22.0 ⁇ 7.2 and 24.7 ⁇ 10.9.
  • 12 is the variation necessary to regain a normalized TWL.
  • Lactobacillus paracasei CNCM 1-2116 allows maintenance of a rapid reconstruction of the barrier function, which is in all cases faster than the treatments with the placebo.
  • the volunteers who underwent the treatment with Lactobacillus paracasei CNCM 1-2116 showed a significant decrease in skin reactivity during the treatment phase. Furthermore, after impairment by "tape strippings", the rate of recovery of the barrier function was significantly faster in the case of the volunteers who underwent the treatment with Lactobacillus paracasei CNCM 1-2116 than in the case of the volunteers who received the placebo.

Abstract

The present invention relates to the cosmetic use of an effective amount of at least one microorganism, especially a probiotic microorganism, or a fraction thereof,as an agent for preventing the appearance and/or for treating the manifestation of sensations of discomfort and/or of cutaneous signs associated with a surface skin treatment or an invasive treatment for aesthetic purposes.

Description

Cosmetic use of microorganisms
The present invention relates to the field of topical products, food supplements or functional foods intended for skincare.
The invention more particularly relates to the cosmetic use of at least one microorganism, especially a probiotic microorganism, or a fraction thereof, as an agent for preventing the appearance and/or for treating the manifestation of sensations of discomfort and/or of cutaneous signs associated with a surface skin treatment, especially of aggressive nature, or with an invasive treatment for aesthetic purposes.
Nowadays, a very large number of treatments exist, possibly concerning aesthetic surgery, for enhancing the appearance of human beings. These treatments, which will be referred to hereinbelow as treatments for aesthetic purposes, may act in many ways, and may consist, for example, in effacing or masking certain skin imperfections, refining the silhouette, or alternatively attenuating or even effacing the signs of ageing.
Non-limiting illustrations of such treatments that may especially be mentioned include chemical peeling treatments, laser treatments, filling injections, or aesthetic surgery operations.
For obvious reasons, such treatments for aesthetic purposes have an action which, although controlled, may be irritative, especially on the surface of the skin. The reason for this is that during these treatments, the skin is generally impaired and cutaneous side reactions that are undesirable to the user may occur.
In general, these undesirable side reactions may occur in two aspects, namely in the form of sensations of discomfort experienced on the skin and/or by the appearance of cutaneous signs, defined as follows.
For the purposes of the invention, the expression "sensation of discomfort" covers any unpleasant sensation, or even pain, which is undesirable to the user.
As regards the cutaneous signs, they may be a matter of bleaching followed by vesiculation, dyschromia, desquamation, redness, dry patches, inflammatory erythema, oedema and/or pimples.
Similarly, more or less deep damage of the epidermis, or even impairment in the cutaneous barrier function, may be observed.
There is thus still a need for novel agents for effectively preventing and/or treating the undesirable side effects associated with the abovementioned treatments for aesthetic purposes and especially for enabling, if necessary, reconstitution of the cutaneous barrier function.
The object of the present invention is, precisely, to satisfy this need.
It is known practice, for example, to use microorganisms for skincare. To this end, document WO 2006/07922 describes compositions for treating sensitive skin using, as active agent, a combination of a Lactobacillus paracasei or casei microorganism and of a Bifidobacterium longum or Bifidobacterium lactis microorganism.
As regards FR 2 872 047, this document describes a combination of a microorganism with a divalent mineral cation. FR 2 889 057, for its part, discloses a topical composition comprising a microorganism in combination with a polyunsaturated fatty acid and/or a polyunsaturated fatty acid ester, which is useful for treating sensitive skin.
WO 02/28402 describes, for its part, the use of probiotic microorganisms for regulating cutaneous hypersensitivity reactions, for instance inflammatory and allergic reactions.
Finally, WO 03/070 260 concerns the use of probiotic microorganisms for skin photoprotection purposes.
The inventors have found, unexpectedly, that the use of an effective amount of at least one microorganism, especially a probiotic microorganism, or a fraction thereof, proves to be most particularly effective for preventing the appearance and/or for treating the manifestation of sensations of discomfort and/or of cutaneous signs, or even an impairment in the cutaneous barrier function, associated with a surface skin treatment or an invasive treatment for aesthetic purposes.
Specifically, the inventors have been able to demonstrate that the use under consideration according to the invention makes it possible especially to restore the homeostasis of a skin tissue, or even to reconstitute the barrier function, if necessary.
They have especially found that the use under consideration according to the invention can significantly prevent the appearance and/or treat the undesirable side effects associated with a surface skin treatment of aggressive nature or an invasive treatment for aesthetic purposes.
Thus, according to a first of its aspects, the present invention relates to the cosmetic use of an effective amount of at least one microorganism, especially a probiotic microorganism, or a fraction thereof, as an agent for preventing the appearance of and/or for treating skin disorders especially of the type such as sensations of discomfort and/or cutaneous signs associated with a surface skin treatment or an invasive treatment for aesthetic purposes.
According to one embodiment, the sensation of discomfort may be a dysaesthesic sensation, chosen especially from stinging, tingling, itching or pruritus, burning, a sensation of heating, a sensation of dryness, erythema and/or tautness.
According to one embodiment, the cutaneous sign may be chosen from bleaching followed by vesiculation, dyschromia, desquamation, redness, dry patches, inflammatory erythema, oedema and/or pimples. According to one embodiment of the invention, the sensations of discomfort and/or the cutaneous signs may be associated with, and, for example, be consecutive to, a surface skin treatment for aesthetic purposes, especially as described hereinbelow.
According to another embodiment of the invention, the sensations of discomfort and/or cutaneous signs may be associated with, and, for example, be consecutive to, an invasive treatment for aesthetic purposes, especially as described hereinbelow.
Similarly, the microorganism, especially the probiotic microorganism, or a fraction thereof, under consideration according to the invention may be used as an agent for maintaining and/or restoring the biomechanical properties of the skin, especially in the case of an individual destined to undergo or who has already undergone at least one surface skin treatment and/or at least one invasive treatment for aesthetic purposes.
Thus, as emerges from the tests presented hereinbelow, a treatment with a microorganism in accordance with the invention promotes the recovery and maintenance of the cutaneous barrier function. Thus, the invention also relates to the cosmetic use of an effective amount of at least one microorganism, especially a probiotic microorganism, or a fraction thereof, for promoting the recovery and/or maintenance of a cutaneous barrier function that is impaired or liable to be impaired by a surface skin treatment or an invasive treatment for aesthetic purposes. According to another of its aspects, the invention also relates to the use of an effective amount of at least one microorganism, especially a probiotic microorganism, or a fraction thereof, for the preparation of a composition, especially a cosmetic and/or therapeutic composition, for preventing the appearance of and/or for treating skin disorders especially of the type such as sensations of discomfort and/or cutaneous signs associated with a surface skin treatment or an invasive treatment for aesthetic purposes.
The invention is also directed towards the use of an effective amount of at least one microorganism, especially a probiotic microorganism, or a fraction thereof, for the preparation of a composition for promoting the recovery and/or maintenance of a cutaneous barrier function that is impaired or liable to be impaired by a surface skin treatment or an invasive treatment for aesthetic purposes.
According to another of its aspects, the present invention also relates to a cosmetic treatment process comprising at least one step of administering to an individual an effective amount of at least one microorganism, especially a probiotic microorganism, or a fraction thereof, the said process being intended to be performed before or after the application to the said individual of at least one surface skin treatment and/or at least one invasive treatment for aesthetic purposes.
According to one embodiment, it may be a cosmetic process for preparing the skin of an individual destined to undergo at least one surface skin treatment and/or at least one invasive treatment for aesthetic purposes, comprising at least one step of administering to the said individual an effective amount of at least one microorganism, especially a probiotic microorganism, or a fraction thereof.
In this case, the administration under consideration according to the invention may be useful for preventing the appearance of sensations of discomfort and/or cutaneous signs associated with the said treatment for aesthetic purposes.
According to another embodiment, it may be a cosmetic process for smoothing the skin of an individual who has undergone at least one surface skin treatment and/or at least one invasive treatment for aesthetic purposes, comprising at least one step of administering to the said individual an effective amount of at least one microorganism, especially a probiotic microorganism, or a fraction thereof.
According to the latter embodiment, the process according to the invention may especially be applied to an individual with damaged skin, especially a cutaneous barrier function that has been impaired as a result of the said treatment for aesthetic purposes.
For the purposes of the present invention, the term "preventing" means reducing the risk of occurrence of the manifestation under consideration. Unless otherwise indicated, in the context of the invention, the term "skin" means any cutaneous surface of the body, including the skin and broadened to the scalp and to the mucous and semi-mucous membranes.
For the purposes of the present invention, the term "effective amount" means an amount that is sufficient to obtain the expected effect.
The microorganism, especially the probiotic microorganism, or a fraction thereof, under consideration according to the invention may be formulated in cosmetic or dermatological compositions.
According to one embodiment, the use or the process according to the invention may comprise the administration of at least one microorganism, especially a probiotic microorganism, or a fraction thereof, or of compositions comprising the same, topically, orally or parenterally, preferably topically or orally.
The term "topically" means an administration of the microorganism, especially the probiotic microorganism, or a fraction thereof, or of compositions comprising the same, by application to the skin, as defined above.
According to another embodiment, the use or the process according to the invention may comprise the administration of at least one microorganism, especially a probiotic microorganism, or a fraction thereof, or of compositions comprising the same, aerially or subcutaneously. The subcutaneous administration may especially be performed using a syringe.
Treatments for aesthetic purposes
For the purposes of the present invention, the term "treatment for aesthetic purposes" means any treatment for remedying an imperfection deemed as being unsightly, and more generally any treatment for beautifying, i.e. for enhancing the appearance of, the individual undergoing such a treatment.
The treatments for aesthetic purposes under consideration according to the invention may more particularly be surface skin treatments or invasive treatments for aesthetic purposes. For the purposes of the invention, the term "surface skin treatment for aesthetic purposes" means treatments liable to have an aggressive nature with regard to the epidermis and especially liable to cause skin irritation. They may especially be chemical peeling treatments and laser treatments. The term "peeling" conventionally denotes a controlled action of irritation of the surface of the skin with a chemical substance or via a physical process.
An operation of peeling type may consist, for example, in applying to the skin a chemical substance for the purpose of bringing about limited and controlled destruction of the epidermis and of the upper layers of the dermis, in order to improve certain disorders of the cutaneous appearance.
Within a matter of years, the panoply of peeling treatments has been considerably modified. The following may be distinguished: surface peeling treatments, which have for a long time been dominated by fruit acids: CC- hydroxy acids (AHAs) and, among those, gly colic acid; peeling with trichloroacetic acid, which remains the panacea of medium- level peeling treatments, and deep peeling treatments performed with phenol, in particular for treating deep lesions. The advantage of surface peeling treatments is that they are very easy to use and that they lead to no desocialization due to their simple follow-ups, making them compatible with the continuation of socio-professional activity.
They are suited to aesthetic procedures: surface wrinkles and fine lines, the complexion, skin imperfections of retentional acne. A surface peeling treatment targets the epidermis and is based on a surface attack of the skin. It affects the epidermis either partially or entirely. It may concern only the stratum corneum (SC) or may go as far as the stratum granulosum or the basal layer depending on the type of agent used, its concentration, the number of applications and the prior degreasing of the skin. This type of peeling treatment is of little efficacy when it is applied only once.
In general, it requires several applications and the whole procedure may take from several weeks to months.
In particular, the AHAs used for surface peeling treatments are keratolytic but do not modify the keratin of corneocytes. They impair the membrane of the corneocytes, giving it a serrated contour, they cause ruptures in the lipid envelope of the corneocytes and target the corneodesmosomes and the desmo somes: they thus cause desquamation in large plaques. In a peeling treatment, they require an acidic pH to have optimum activity. They are also used at higher doses in peeling treatments. Glycolic acid or hydroxyacetic acid is the most well known of these agents.
GIy co lie acid is the smallest member of the AHAs (chain containing two carbon atoms), and its size thus enables it to penetrate easily into the horny layer. In the same respect as citric acid (citrus fruit), malic acid (green apple), tartaric acid (grape) or lactic acid (milk, red berries), glycolic acid is present in nature.
The properties of glycolic acid are associated with the activation of desquamation. It thus promotes exfoliation of the dead surface cells, which takes place less efficiently with age, in order to restore the qualities of the skin surface (clarity, luminosity, uniformity of complexion, softness, smoothness of the skin relief and action on skin imperfections). Furthermore, it helps towards combating the hyperkeratinization of skin imperfections and thus contributes towards reducing them.
The higher the concentration of glycolic acid, the greater the efficiency. Such a peeling treatment should be neutralized in order to avoid excessive skin irritation. The neutralization is performed with sodium hydroxide or sodium bicarbonate. In parallel with the abovementioned peeling treatments which may be termed
"chemical" with regard to the chemical products they use, a technique referred to hereinbelow as physical peeling has also been developed, involving the use of ablative and non-ablative lasers.
The first ablative lasers, produced with pulsed or scanned CO2 lasers, have the immediate effect of vaporizing (or ablating) the epidermis and often the upper part of the dermis. A strip of the subjacent dermis is generally also the site of a thermal lesion with denaturation and contraction of collagen. During the cicatrization phase, re-epithelization takes place from the hair follicles and other appendages in addition to an upper dermal strip ("collagen remodelling"). The latest generation of lasers uses a system for transforming the laser beam into a multitude of spaced-out beams in order to produce on the skin spaced-out impacts, thus maintaining areas of unimpaired healthy skin between the affected areas.
For the purposes of the invention, the term "laser treatment" means any treatment for aesthetic purposes using a laser, including the physical peeling treatments described previously.
Examples of laser treatments that may thus also be mentioned include laser depilation; laser treatment of angiomas; laser treatment of redness, especially of erythrosis or rosacea; laser treatment of lentigo, especially actinic lentigo; laser treatment of tattoos; or laser treatment of wrinkles.
The various lasers that may be used for these treatments will not be the subject of a detailed description herein. Examples of invasive treatments for aesthetic purposes that may be mentioned include filling injections and aesthetic surgery operations.
For the purposes of the invention, the term "filling injection" is intended to denote any injection of compounds intended to afford an aesthetic effect.
The injection methods may be of retrograde tracing or multi-puncture type. It may especially concern an injection of collagen, an injection of hyaluronic acid or an injection of type A botulinum toxin (sold under the name Botox®).
These compounds may be injected into the skin, and thus create volume, giving an appearance of vitality and good health.
When injected under a wrinkle, they in particular perform lifting of the skin, reswelling the tissues and restoring the skin's smooth, natural and taut appearance.
The term "lift" generally denotes all the operations intended to correct collapse of the skin, for example collapse of the cheekbones and of the hollows in the middle of the cheeks.
A lift may thus also be performed, where appropriate, via an aesthetic surgery operation.
For the purposes of the invention, the term "aesthetic surgery" is intended to denote surgery directed especially towards correcting congenital unsightly physical features (nose, ears or chin) or unsightly physical features acquired at puberty (mammary hypotrophy, or localized excess fat), as a result of pregnancy (deformation of the abdominal wall) or as a result of ageing (face, eyebrows, neck or breasts).
Aesthetic surgery operations that may thus also be mentioned include, in a non- limiting manner, blepharoplasty, abdominal plasty (or abdominoplasty), rhinoplasty, mammary plasty, liposuction and lipostructure.
Microorganisms, especially probiotic microorganisms
The microorganisms that are suitable for use in the invention are microorganisms that may be administered without risk to man or animals. In particular, at least one microorganism of "probiotic" type is used in the present invention.
For the purposes of the present invention, the term "probiotic microorganism" means a live microorganism which, when consumed in adequate amount, has a positive effect on the health of its host ("Joint FAO/WHO Expert Consultation on Evaluation of Health and Nutritional Properties of Probiotic in Food Including Powder Milk with Live Lactic Acid Bacteria, 6 October 2001"), and which may in particular improve the intestinal microbial equilibrium.
According to one variant of the invention, this microorganism is used in an isolated form, i.e. not mixed with one or more compound(s) liable to be associated therewith in its medium of origin.
For the purposes of the invention, the term "fraction" more particularly denotes a fragment of the said microorganism that has efficacy in treating dry skin by analogy with the said whole microorganism. The microorganisms that are suitable for use in the invention may be chosen especially from ascomycetes such as Saccharomyces, Yarrowia, Kluyveromyces, Torulaspora, Schizosaccharomyces pombe, Debaromyces, Candida, Pichia, Aspergillus and Penicillium, bacteria of the genera Bifidobacterium, Bacteroides, Fusobacterium, Melissococcus, Propionibacterium, Enter ococcus, Lactococcus, Staphylococcus, P eptostrepococcus , Bacillus, Pediococcus, Micrococcus, Leuconostoc, Weissella, Aerococcus, Oenococcus and Lactobacillus, and mixtures thereof.
As ascomycetes that are most particularly suitable for use in the present invention, mention may be made in particular of Yarrowia lipolitica and Kluyveromyces lactis, and also Saccharomyces cerevisiae, Torulaspora, Schizosaccharamyces pombe, Candida and Pichia.
As regards the probiotic microorganisms, the following bacterial and yeast genera are generally used: lactic acid bacteria: which produce lactic acid by fermentation of sugar. According to their morphology, they are divided into two groups: • Lactobacillus species: Lactobacillus acidophilus, amylovorus, casei, rhamnosus, brevis, crispatus, delbrueckii (subsp bulgaricus, lactis), fermentum, helveticus, gallinarum, gasseri johnsonii, paracasei, plantarum, reuteri, salivarius, alimentarius, curvatus, casei subsp. casei, sake
• Gocci: Enterococcus (faecalis, faecium), Lactococcus lactis (subsp lactis or cremoris), Leuconstoc mesenteroides subsp dextranicum,
Pediococcus acidilactici, Sporolactobacillus inulinus, Streptococcus salvarius subsp. Thermophilus, Streptococcus thermophilus,
Staphylococccus carnosus, Staphylococcus xylosus bifidobacteria or Bifidobacterium species: Bifidobacterium adolescentis, animalis, bifidum, breve, lactis, longum, infantis, pseudocatenulatum, yeasts: Saccharomyces (cerevisiae or boulardii), - other sporulating bacteria: Bacillus (cereus var toyo or subtilis), Bacillus coagulans, Bacillus licheniformis, Escherichia coli strain nissle, Propionibacterium freudenreichii, and mixtures thereof.
Lactic acid bacteria and bifidobacteria are the probiotics most commonly used. Specific examples of probiotic microorganisms are Bifidobacterium adolescentis,
Bifidobacterium animalis, Bifidobacterium bifidum, Bifidobacterium breve,
Bifidobacterium lactis, Bifidobacterium longum, Bifidobacterium infantis, Bifidobacterium pseudocatenulatum, Lactobacillus acidophilus (NCFB 1748) ; Lactobacillus amylovorus,
Lactobacillus casei (Shirota), Lactobacillus rhamnosus (strain GGA Lactobacillus brevis, Lactobacillus crispatus, Lactobacillus delbrueckii (subsp bulgaricus, lactis), Lactobacillus fermentum, Lactobacillus helveticus, Lactobacillus gallinarum, Lactobacillus gasseri,
Lactobacillus johnsonii (CNCM 1-1225), Lactobacillus paracasei, Lactobacillus plantarum, Lactobacillus reuteri, Lactobacillus salivarius, Lactobacillus alimentarius,
Lactobacillus curvatus, Lactobacillus casei subsp. casei, Lactobacillus sake, Lactococcus lactis, Enterococcus (faecalis, faecium), Lactococcus lactis (subspp lactis or cremoris),
Leuconstoc mesenteroides subsp dextranicum, Pediococcus acidilactici,
Sporolactobacillus inulinus, Streptococcus salvarius subsp. Thermophilus, Streptococcus thermophilus, Staphylococccus carnosus, Staphylococcus xylosus, Saccharomyces
(cerevisiae or boulardii), Bacillus (cereus var toyo or subtilis), Bacillus coagulans, Bacillus licheniformis, Escherichia coli strain nissle and Propionibacterium freudenreichii, and mixtures thereof.
Preferably, the probiotic microorganism may be chosen from: Lactobacillus acidophilus, Lactobacillus alimentarius, Lactobacillus curvatus, Lactobacillus delbruckii (subsp. bulgaricus lactis), Lactobacillus gasseri, Lactobacillus johnsonii, Lactobacillus reuteri, Lactobacillus rhamnosus (strain GG), Lactobacillus sake, Lactococcus lactis, Streptococcus thermophilus, Staphylococccus carnosus and Staphylococcus xylosus, and mixtures thereof. These microorganisms may be formulated in the form of powders, i.e. in a dry form, or in the form of suspensions or solutions.
More particularly, they are probiotic microorganisms derived from the group of lactic acid bacteria, especially such as Lactobacillus and/or Bifidobacterium. As illustrations of these lactic acid bacteria, mention may be made more particularly of Lactobacillus johnsonii, Lactobacillus reuteri, Lactobacillus rhamnosus, Lactobacillus paracasei, Lactobacillus casei or Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium animalis, Bifidobacterium lactis, Bifidobacterium infantis, Bifidobacterium adolescentis or Bifidobacterium pseudocatenulatum and mixtures thereof, and preferably Lactobacillus johnsonii, Lactobacillus reuteri, Lactobacillus rhamnosus and Lactobacillus paracasei, and mixtures thereof.
The species that are most particularly suitable for use are Lactobacillus johnsonii, Lactobacillus paracasei, Bifidobacterium adolescentis, Bifidobacterium longum and Bifidobacterium lactis NCC 2818, which were deposited, respectively, according to the treaty of Budapest, at the Institut Pasteur (28, rue du Docteur Roux, F-75024 Paris cedex 15) on 30/06/92, 12/01/99, 15/04/99, 15/04/99 and 07/06/05 under the following designations CNCM 1-1225, CNCM 1-2116, CNCM 1-2168 and CNCM 1-2170 and CNCM 1-3446, and the genus Bifidobacterium longum (BB 536), and mixtures thereof.
According to one particular embodiment, the probiotic microorganism is of the genus Lactobacillus species, in particular the species Lactobacillus johnsonii and more particularly of the species Lactobacillus paracasei, or a fraction thereof.
They may especially be the species Lactobacillus johnsonii and Lactobacillus paracasei deposited, respectively, according to the treaty of Budapest, at the Institut Pasteur (28, rue du Docteur Roux, F-75024 Paris cedex 15) on 30/06/92 and 12/01/99 under the designations CNCM 161225 and CNCM 1-2116.
According to one embodiment, the probiotic microorganism is the strain of Lactobacillus paracasei deposited, according to the treaty of Budapest, at the Institut Pasteur (28, rue du Docteur Roux, F-75024 Paris cedex 15) on 12/01/99 under the designation CNCM 1-2116.
According to one particular embodiment, a composition according to the invention may comprise at least two different microorganisms, especially probiotic microorganisms, and/or fractions thereof. The microorganism(s) may be included in the composition according to the invention in a live, semi-active or inactivated, dead form.
It (they) may also be included in the form of fractions of cell components. The microorganism(s) or fraction(s) may also be introduced in the form of a freeze-dried powder, a culture supernatant and/or, where appropriate, in a concentrated form. In general, the compositions according to the invention may comprise from
0.00001% to 20% by weight, in particular from 0.001% to 20% by weight and more particularly from 0.01% to 10% by weight of microorganism(s), especially probiotic microorganism(s), relative to the total weight of the composition.
It may be advantageous to use these microorganisms in inactivated or even dead form, and more particularly in the form of a lysate.
Such a lysate may be obtained from the cell lysis of the microorganism concerned, according to a conventional method.
The probiotic microorganism(s) in the form of a disintegrated lysate in suspension may be formulated in a suitable support in a proportion of less than 20% by weight, in particular in a proportion of from 0.0001% to 20% by weight and more particularly in a proportion of from 0.01% to 10% by weight relative to the total weight of the said support.
When they are live, the microorganisms and/or the fractions thereof may be formulated in a suitable support in an amount equivalent to at least 103 cfu/g, in particular at doses ranging from 105 to 1015 cfu/g and more particularly from 107 to 1012 cfu/g of support.
Thus, the compositions according to the invention generally comprise from 103 to 1012 cfu, in particular from 105 to 1010 cfu and more particularly from 107 to 109 cfu of live microorganisms, especially probiotic microorganisms, per gram of support. The compositions according to the invention may be in any galenical form normally available for the selected mode of administration.
The support may be of diverse nature according to the type of composition under consideration. As more particularly regards compositions for external topical administration, they may be aqueous, aqueous-alcoholic or oily solutions, dispersions of the solution type or dispersions of the lotion or serum type, emulsions of liquid or semi- liquid consistency of the milk type, suspensions or emulsions of the cream type, aqueous or anhydrous gels, microemulsions, microcapsules, microparticles, or vesicular dispersions of ionic and/or nonionic type.
These compositions are prepared according to the usual methods. In a known manner, galenical forms dedicated to topical administration may also contain adjuvants that are common in cosmetics, pharmaceutics and/or dermatology, such as hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic active agents, preserving agents, antioxidants, solvents, fragrances, fillers, screening agents, bactericides, odour absorbers and dyestuffs. The amounts of these various adjuvants are those conventionally used in the field under consideration, for example from 0.01% to 20% of the total weight of the composition. Depending on their nature, these adjuvants may be introduced into the fatty phase and/or into the aqueous phase.
As fatty substances that may be used in the invention, mention may be made of mineral oils, for instance hydrogenated polyisobutene and liquid petroleum jelly, plant oils, for instance a liquid fraction of shea butter, sunflower oil and apricot kernel oil, animal oils, for instance perhydrosqualene, synthetic oils, especially purcellin oil, isopropyl myristate and ethylhexyl palmitate, unsaturated fatty acids and fluoro oils, for instance perfluoropolyethers. It is also possible to use fatty alcohols, fatty acids, for instance stearic acid and, for example, waxes, especially paraffin wax, carnauba wax and beeswax. Silicone compounds may also be used, for instance silicone oils, for example cyclomethicone and dimethicone, silicone waxes, silicone resins and silicone gums. As emulsifϊers that may be used in the invention, examples that may be mentioned include glyceryl stearate, polysorbate 60, the mixture of cetylstearyl alcohol/cetylstearyl alcohol oxyethylenated with 33 mol of ethylene oxide, sold under the name Sinnowax AO® by the company Henkel, the mixture of PEG-6/PEG-32/glycol stearate sold under the name Tefose® 63 by the company Gattefosse, PPG-3 myristyl ether, silicone emulsifϊers such as cetyldimethicone copolyol and sorbitan monostearate or tristearate, PEG-40 stearate, and oxyethylenated (20 EO) sorbitan monostearate.
As solvents that may be used in the invention, mention may be made of lower alcohols, especially ethanol and isopropanol, and propylene glycol. The composition of the invention may also advantageously contain a spring and/or mineral water, chosen especially from Vittel water, waters from the Vichy Basin, and Ia Roche Posay water.
In the case of an oral use in accordance with the invention, the use of an ingestible support is preferred.
The ingestible support may be of diverse nature according to the type of composition under consideration.
Tablets or lozenges, oral supplements in dry form and oral supplements in liquid form are thus especially suitable for use as pharmaceutical or food supports. They may be, for example, food supplements, the formulation of which may be performed via the usual processes for especially producing coated tablets, gel capsules, gels, emulsions, tablets, wafer capsules and hydrogels allowing controlled release.
In particular, the microorganism according to the invention may be incorporated into any other form of food supplement or enriched food, for example food bars or compacted or non-compacted powders. The powders may be diluted in water, soda, dairy products or soybean derivatives, or may be incorporated into food bars.
The microorganism, especially the probiotic microorganism, or a fraction thereof, may moreover be formulated with the usual excipients and components for such oral compositions or food supplements, i.e. especially fatty and/or aqueous components, humectants, thickeners, preserving agents, texture agents, taste agents and/or coating agents, antioxidants, preserving agents and dyes that are common in the food sector.
The formulating agents and excipients for oral compositions, and especially for food supplements, are known in this field and will not be the subject of a detailed description herein. Milk, yoghurt, cheese, fermented milks, milk-based fermented products, ice creams, cereal-based products or fermented cereal-based products, milk-based powders, infant and baby formulae, food products of confectionery, chocolate or cereal type, animal feed in particular for pets, tablets, gel capsules or lozenges, liquid bacterial suspensions, oral supplements in dry form and oral supplements in liquid form are especially suitable as pharmaceutical or food supports.
Irrespective of the mode of administration under consideration, the effective amount of the microorganism, especially the probiotic microorganism, or a fraction thereof, may also be advantageously combined with at least one other active agent. As active agents that may be used, mention may be made of vitamin A, B3, B5, B6, B8, C, D, E or PP, curcuminoids, carotenoids, polyphenol compounds and mineral compounds, sugars, amino acids, sulfur-containing amino acids, 3 and 6 polyunsaturated fatty acids, taurine and phytosterols. It is possible in particular to use an antioxidant complex comprising vitamins C and E, and at least one carotenoid, especially a carotenoid chosen from β-carotene, lycopene, astaxanthin, zeaxanthin and lutein, flavonoids such as catechins, proanthocyanidins, anthocyanins, ubiquinones, coffee extracts containing polyphenols and/or diterpenes, extracts of chicory, extracts of ginkgo biloba, extracts of grape rich in proanthocyanidins, extracts of pimento, extracts of soybean, other sources of flavonoids having antioxidant properties, fatty acids, prebiotic agents, taurine, resveratrol, selenium- containing amino acids, and glutathione precursors.
Among the flavonoids, catechins and PCOs (procyannidol oligomers) are preferably chosen. Proteins or protein hydro lysates, amino acids, polyols, especially of C2 to C10, for instance glycerol, sorbitol, butylene glycol and polyethylene glycol, urea, allantoin, sugars and sugar derivatives, water-soluble vitamins, starch, and bacterial or plant extracts such as those of Aloe vera, may be used more particularly as hydrophilic active agents in the topical galenical forms. As regards the lipophilic active agents, retinol (vitamin A) and derivatives thereof, tocopherol (vitamin E) and derivatives thereof, ceramides, essential oils and unsaponifϊable materials (tocotrienol, sesamine, gamma-oryzanol, phytosterols, squalenes, waxes and terpenes) may be used.
As active agents that may also be combined with the microorganism, especially the probiotic microorganism, or a fraction thereof, and that are suitable for topical use but more particularly suited to an oral galenical formulation, any ingredient commonly used and/or permitted, especially active agents for preventing and/or treating skin complaints, may also be considered.
Illustrations that may be mentioned include vitamins, minerals, essential lipids, trace elements, polyphenols, flavonoids, phyto-oestrogens, antioxidants such as lipoic acid and coenzyme QlO, carotenoids, prebiotic agents, proteins and amino acids, monosaccharides and polysaccharides, amino sugars, phytosterols and triterpenic alcohols of plant origin. They are, in particular, vitamins A, C, D, E and PP and group B vitamins. Among the carotenoids, β-carotene, lycopene, lutein, zeaxanthin and astaxanthin are preferably chosen. The minerals and trace elements particularly used are zinc, calcium, magnesium, copper, iron, iodine, manganese, selenium and chromium (III). Among the polyphenols, polyphenols from grape, from tea, from olive, from cocoa, from coffee, from apple, from blueberry, from elderberry, from strawberry, from cranberry and from onion are also selected in particular. Preferably, among the phyto-oestrogens, isoflavones in free or glycosylated form are selected, such as genistein, daidzein, glycitein or lignans, in particular those from flax and from Schizandra chinensis. The amino acids or the peptides and proteins containing them, such as taurine, threonine, cysteine, tryptophan or methionine. The lipids preferably belong to the group of oils containing monounsaturated and polyunsaturated fatty acids such as oleic acid, linoleic acid, α-linolenic acid, γ- linolenic acid, stearidonic acid, long-chain fish omega-3 fatty acids such as EPA and DHA, and conjugated fatty acids derived from plants or animals, such as CLAs (conjugated linoleic acid).
Thus, in particular, when the microorganism, especially the probiotic microorganism, or a fraction thereof, is intended for oral administration, it may also be combined with at least one nutritional active agent chosen from lycopene, vitamin C, vitamin E and polyphenol compounds. The microorganism, especially the probiotic microorganism, or a fraction thereof, or a combination according to the invention, may also be combined with other nutritional active agents chosen from: anti-ageing nutritional active agents, such as food antioxidants, nutrients with free-radical-scavenging properties and cofactors of antioxidant endogenous enzymes, vitamins A, C and E, carotenoids, xanthophylls, isoflavones, certain minerals such as zinc, copper, magnesium or selenium, lipoic acid, coenzyme QlO, superoxide dismutase (SOD) or taurine. Among the anti-ageing active agents, mention may be made especially of the unsaponifϊable fractions extracted from lipids of plant origin, Aloe vera, native or hydro lysed marine collagen, and plant or marine oils rich in omega-3 and omega-6 fatty acids (including γ-linolenic acid), photoprotective nutritional active agents such as: antioxidants and free- radical scavengers, vitamins A, C and E, carotenoids, xanthophylls, certain minerals such as zinc, copper, magnesium or selenium, coenzyme QlO and superoxide dismutase (SOD), nutritional ingredients with moisturizing or immunomodulating properties, such as an extract of Polypodium leucotomos, and plant or marine oils rich in omega-3 and omega-6 fatty acids, including γ-linolenic acid, nutritional active agents that are active on the clinical signs of the menopause (for example hot flushes, etc.), such as isoflavones, lignans, DHEA, extracts of yam, of sage or of hop, calcium, magnesium, protein hydro lysates, and plant or marine oils rich in omega-3 fatty acids, nutritional ingredients used in the slimming sector, such as extracts of green tea, mate, common horse chestnut, cola, caffeine, theobromine, synephrine, bromelain, ephedra, Citrus aurantium, calcium, hoodia, garcinia, chitosan, plant fibre (from cactus, apple, pineapple, etc.), fennel, blackcurrant, meadowsweet and black radish.
The cosmetic treatment process of the invention may be performed especially by orally and/or topically administering at least an effective amount of at least one microorganism, especially a probiotic microorganism, or a fraction thereof. The topical administration consists of the external application to the skin of cosmetic and/or dermato logical compositions according to the usual technique for using these compositions.
The cosmetic process according to the invention may be performed by topical administration, for example daily, of cosmetic and/or dermato logical compositions, which may be formulated, for example, in the form of gels, lotions or emulsions.
The oral administration consists in ingesting in one or more intakes an oral composition as defined above.
According to one variant, the cosmetic process comprises at least one step of oral administration of an effective amount of at least one microorganism, especially a probiotic microorganism, or a fraction thereof, and at least one step of topical administration of an effective amount of at least one microorganism, especially a probiotic microorganism, or a fraction thereof.
The process according to the invention may comprise a single administration. According to another embodiment, the administration is repeated, for example two to three times daily for one day or more and generally for an extended period of at least 4 weeks, or even 4 to 15 weeks, with, where appropriate, one or more periods of stoppage. In the description and in the examples that follow, unless otherwise mentioned, the percentages are weight percentages and the ranges of values written in the form "between ... and ..." include the stated lower and upper limits.
The ingredients are mixed, before being formed, in the order and under conditions that may be readily determined by those skilled in the art.
The examples below are given as non-limiting illustrations of the field of the invention.
Example 1 : Single-dose gel
Figure imgf000019_0001
A dose of from 200 to 400 ml per day may be taken.
Example 2: Capsule
Figure imgf000019_0002
One to three of these capsules may be taken per day.
Example 3
A vitamin complex comprising 60 mg of vitamin C, 100 μg of vitamin E and 6 mg of β-carotene is added to the formulation of Example 2. Example 4
A vitamin complex comprising 100 mg of vitamin C, 100 μg of vitamin E and mg of lycopene per capsule is added to the formulation of Example 2.
Example 5 : Body lotion in spray form
(weight%)
Lactobacillus paracasei (CNCM 1-2116) 5.00
Antioxidant 0.05
Isopropanol 40.00
Preserving agent 0.35
Water qs 100.00
Example 6: Facial care cream
(weight%)
Lactobacillus johnsonii (CNCM 1-1225) 5.00
Antioxidant 0.05
Isopropanol 40.00
Glyceryl stearate 1.00
Cetylstearyl alcohol/cetylstearyl alcohol oxyethylenated with
33 mol of EO (Sinnowax AO sold by the company Henkel) 3.00
Cetyl alcohol 1.00
Dimethicone (DC 200 Fluid sold by the company Dow Corning) 1.00
Liquid petroleum jelly 6.00
Isopropyl myristate (Estol IPM 1514 sold by Uniqema) 3.00
Antioxidant 0.05
Glycerol 20.00
Preserving agent 0.30
Water qs 100.00 Example 7: Facial care gel
(weight%)
Lactobacillus paracasei (CNCM 1-2116) 1010 cfu Antioxidant O .05 Vitamin C 2 .50
Antioxidant O .05 Isopropanol 40 .00 Preserving agent 0 .30 Water qs 100 .00
Example 8: Effect of a food supplement comprising a microorganism in accordance with the invention on cutaneous reactivity and reconstitution of the barrier function
The strain Lactobacillus paracasei CNCM 1-2116 was tested alone, in a double-blind randomized study.
64 women with reactive skin were divided into two groups:
- a first group of 32 women, to whom was administered a placebo (maltodextrin, referred to hereinbelow as "product A"), and
- a second group of 32 women, to whom was administered Lactobacillus paracasei CNCM 1-2116 alone (referred to hereinbelow as "product B").
These food supplements were administered orally, for 58 days, at a rate of 1010 cfu/day.
1. Study of the cutaneous reactivity
The cutaneous reactivity of the two groups of women was measured according to the following test with capsaicin, in which the concentration of capsaicin perceived makes it possible to assess the reactivity of the skin.
The following capsaicin solutions of increasing concentration Ci to Cs were used:
Figure imgf000022_0001
Capsaicin of > 97% purity, sold by Fluka, is used.
The capsaicin solutions were applied to the nasolabial folds, from the nostril wall to the corner of the mouth, by wiping with a single-use cotton-tipped applicator (Societe Industrielle du Bois) impregnated with an average volume of 0.2 ml of solution and depositing an average volume of 0.02 ml of solution (volumes measured by differential weighing).
The test was performed according to the following steps:
1st step: the nasolabial folds were cleansed/freed of makeup using a gauze impregnated with an aqueous-alcoholic solution containing 10% ethano 1.
2nd step: 1 minute later, the vehicle solution is applied simultaneously to each nostril wall, using a cotton-tipped applicator.
If the individual reports uncomfortable sensations of the type such as irritation, stinging, itching, tautness or heating: the test is stopped.
If the individual does not report any uncomfortable sensations: the study is continued.
3rd step: 2 minutes after step 2, solution Cl of capsaicin and the vehicle are applied simultaneously, under single-blind conditions, to the nasolabial folds, in accordance with a randomization list that sets the application sides.
If the individual reports within 2 minutes 30 seconds of the application a specific sensation, i.e. any type of discriminating sensation relative to the vehicle, that may be of discomfort type or of any other nature (however minor it may be, but lasting for at least 30 seconds) on the side which received Cl, the test is stopped and Cl is attributed to the individual as the capsaicin detection threshold.
If the individual does not report any specific sensation on the side which received Cl, the test is continued with solutions C2 to C5, according to the same protocol.
For each individual, the detected capsaicin concentration is recorded (the test stopping at that concentration).
The table below presents, for each group of women and for each visit, the mean and the standard deviation of the values of the capsaicin solution detected on Dl, D29, D43 and D57.
Figure imgf000023_0001
It is noted that the treatment with product B significantly increases the reactivity threshold at all the visits relative to Dl, and does so up to D57.
The treatment with product B thus significantly increases the reactivity threshold at D57 with a p = 0.01, the threshold increasing up to D43 and then remaining steady.
This increase is gradual and very uniform over time.
The analysis of the results obtained also underlines the fact that the treatment with L. paracasei CNCM 1-2116 alone significantly decreases on D43 the reactivity of the skin relative to the treatment with product A (placebo) (p = 0.04).
Moreover, under placebo, the reactivity threshold of the volunteers varies randomly according to the evaluation day (decrease on D29, increase on D43 and then slight decrease again on D57). In contrast, the volunteers treated with product B show a gradual uniform decrease in their reactivity threshold, resulting at all times in decreases that are significantly different relative to their reactivity threshold on Dl .
Analysis of the contrasts between each visit for each group between Dl and D57, which is reported in the table below, indicates that all the results obtained for product B are significant, whereas only the results obtained over the period D1-D29 are significant for the study of product A.
Figure imgf000024_0001
2. Measurement of the transepidermal water loss (TWL) after repeated "tape strippings" using an evaporimeter
This measurement consists of the repeated application of a strip of dermatological adhesive tape to the skin of the inner face of one of the volunteer's forearms, the operation being recommenced as many times as necessary (repeated tape strippings).
In the context of the present study, a moderate aggression was performed using
25χ25 mm "tape strippings" in order to obtain a TWL value > 15, using 25 mm Blenderm™ (3M) hypoallergenic occlusive adhesive plaster strips.
The measurement of the transepidermal water loss (TWL) was performed before and after each aggression using an EPl evaporimeter (Servomed®) to the stripped part and to an area close to it (controlled area).
At t8h, t24h, t48h and t72h, the inner face of the treated forearm was covered with a dry gauze until the following measurement. The tables below present for each group the TWL value of the stripped area at each measurement evaluation kinetic during the various visits (TOH being the value just after the strippings).
Figure imgf000025_0001
Figure imgf000025_0002
The tables below present for each group the normalized data at the non- stripped areas, expressed as a difference relative to the value at TO (only the means have been reported in this table for the sake of clarity).
Figure imgf000025_0003
Figure imgf000026_0001
Statistical analysis was effected on the rate of repair of the cutaneous barrier, and was performed over the treatment period (from D1-D5 to D57-D61) and over the remanence period (from D57-D61 to D78-D82), the TWL study being spread over 5 days at each visit.
The rate of repair of the cutaneous barrier is estimated by the parameter "d" according to the model: Delta = -d*TWL(0)*log(t+l) in which Delta is the difference in TWL between the stripped area and the control area, calculated according to the following formula:
Delta = (ZTti - ZTtO) - (ZCti - ZCtO) with ZT: value obtained on the stripped area, ZC: value obtained on the control area, tθ: t0 after stripping, ti: at the various measurement times.
a) Treatment period
The results obtained show that the volunteers treated with product B have a significantly faster rate of recovery of their TWL than those treated with product A (placebo) at the end of the treatment period (recovery from 48h for product B versus 72- 96h for the placebo).
b) Remanence period
The volunteers treated with product B continue to have a faster rate of recovery of their TWL value between D64 and D78 when compared with the volunteers receiving the treatment with product A (p = 0.003).
It is observed that a threshold value of -12 corresponds to the TWL value (as an absolute value) that is necessary to return to the TWL value before stripping.
Specifically, the healthy volunteers have a TWL value of between 5.1 ±2.6 and 6.5±2.6, and the performed strippings lead to an increase of their TWL value to between 22.0±7.2 and 24.7±10.9. Thus, 12 is the variation necessary to regain a normalized TWL.
Analysis of the contrasts between the groups between Dl and D57 and D64 and D78 is indicated in the table below.
Figure imgf000027_0001
With the treatment with Lactobacillus paracasei CNCM 1-2116 alone, a faster rate of recovery of the barrier function than with the placebo is observed at the end of the treatment phase.
During the remanence phase, only the treatment with Lactobacillus paracasei CNCM 1-2116 allows maintenance of a rapid reconstruction of the barrier function, which is in all cases faster than the treatments with the placebo.
3. Conclusion
The results show that the administration of Lactobacillus paracasei CNCM I- 2116 has a positive effect on the two main parameters of the study, namely the reactivity of the skin and the reconstruction of the barrier function.
Specifically, the volunteers who underwent the treatment with Lactobacillus paracasei CNCM 1-2116 showed a significant decrease in skin reactivity during the treatment phase. Furthermore, after impairment by "tape strippings", the rate of recovery of the barrier function was significantly faster in the case of the volunteers who underwent the treatment with Lactobacillus paracasei CNCM 1-2116 than in the case of the volunteers who received the placebo.
A decrease as a function of time in the levels of cutaneous hydration factors such as urea and lactate were observed in the case of the volunteers who received the placebo. These factors contribute towards impairing the integrity of the barrier function.
Conversely, these markers were maintained unchanged throughout the study in the case of the volunteers who received Lactobacillus paracasei CNCM 1-2116, which correlates with the previously reported data regarding the reinforcement of the rate of recovery of the barrier function.

Claims

1. Cosmetic use of an effective amount of at least one microorganism, especially a probiotic microorganism, or a fraction thereof, as an agent for preventing the appearance and/or for treating the manifestation of sensations of discomfort and/or cutaneous signs associated with a surface skin treatment chosen from chemical peeling treatments and laser treatments, or an invasive treatment for aesthetic purposes.
2. Use according to the preceding claim, characterized in that the sensation of discomfort is a dysaesthesic sensation especially chosen from stinging, tingling, itching or pruritus, burning, a sensation of heating, a sensation of dryness, erythema and/or tautness.
3. Use according to either of the preceding claims, characterized in that the cutaneous sign is chosen from bleaching followed by vesiculation, dyschromia, desquamation, redness, dry patches, inflammatory erythema, oedema and/or pimples.
4. Use according to any one of claims 1 to 3, characterized in that the sensations of discomfort and/or the cutaneous signs are associated with an invasive treatment for aesthetic purposes especially chosen from filling injections and aesthetic surgery operations.
5. Cosmetic use of an effective amount of at least one microorganism, especially a probiotic microorganism, or a fraction thereof, for promoting the recovery and/or maintenance of a cutaneous barrier function that is impaired or liable to be impaired by a surface skin treatment or an invasive treatment chosen from chemical peeling treatments and laser treatments, for aesthetic purposes.
6. Use of an effective amount of at least one microorganism, especially a probiotic microorganism, or a fraction thereof, for the preparation of a composition for preventing the appearance and/or for treating the manifestation of sensations of discomfort and/or of cutaneous signs associated with a surface skin treatment chosen from chemical peeling treatments and laser treatments, or an invasive treatment for aesthetic purposes.
7. Use of an effective amount of at least one microorganism, especially a probiotic microorganism, or a fraction thereof, for the preparation of a composition for promoting the recovery and/or maintenance of a cutaneous barrier function that is impaired or liable to be impaired by a surface skin treatment chosen from chemical peeling treatments and laser treatments, or an invasive treatment for aesthetic purposes.
8. Use according to any one of the preceding claims, characterized in that the said microorganism is chosen from ascomycetes such as Saccharomyces, Yarrowia, Kluyveromyces, Torulaspora, Schizosaccharomyces pombe, Debaromyces, Candida, Pichia, Aspergillus and Penicillium, bacteria of the genera Bifidobacterium, Bacteroides, Fusobacterium, Melissococcus, Propionibacterium, Enterococcus, Lactococcus, Staphylococcus, Peptostrepococcus, Bacillus, Pediococcus, Micrococcus, Leuconostoc, Weissella, Aerococcus, Oenococcus and Lactobacillus, and mixtures thereof.
9. Use according to any one of the preceding claims, characterized in that the microorganism is chosen from Bifidobacterium adolescentis, Bifidobacterium animalis, Bifidobacterium bifidum, Bifidobacterium breve, Bifidobacterium lactis, Bifidobacterium longum, Bifidobacterium infantis, Bifidobacterium pseudocatenulatum, Lactobacillus acidophilus (NCFB 1748) ; Lactobacillus amylovorus, Lactobacillus casei (Shirota), Lactobacillus rhamnosus (strain GG), Lactobacillus brevis, Lactobacillus crispatus, Lactobacillus delbrueckii (subsp bulgaricus, lactis), Lactobacillus fermentum, Lactobacillus helveticus, Lactobacillus gallinarum, Lactobacillus gasseri, Lactobacillus johnsonii (CNCM 1-1225), Lactobacillus paracasei, Lactobacillus plantarum, Lactobacillus reuteri, Lactobacillus salivarius, Lactobacillus alimentarius, Lactobacillus curvatus, Lactobacillus casei subsp. casei, Lactobacillus sake, Lactococcus lactis, Enterococcus (faecalis, faecium), Lactococcus lactis (subspp lactis or cremoris), Leuconstoc mesenteroides subsp dextranicum, Pediococcus acidilactici, Sporolactobacillus inulinus, Streptococcus salvarius subsp. Thermophilus, Streptococcus thermophilus, Staphylococccus carnosus, Staphylococcus xylosus, Saccharomyces (cerevisiae or boulardii), Bacillus (cereus var toyo or subtilis), Bacillus coagulans, Bacillus licheniformis, Escherichia coli strain nissle and Propionibacterium freudenreichii, and mixtures thereof.
10. Use according to any one of the preceding claims, characterized in that the microorganism is derived from the group of lactic acid bacteria.
11. Use according to any one of the preceding claims, characterized in that the microorganism is of the species Lactobacillus paracasei, or a fraction thereof, and preferably the Lactobacillus paracasei deposited on 12/01/99 under the designation CNCM 1-2116.
12. Use according to any one of the preceding claims, characterized in that the microorganism, especially the probiotic microorganism, is used in a proportion of from
0.00001% to 20% by weight and more particularly in a proportion of from 0.01% to 10% by weight relative to the total weight of the composition containing it.
13. Use according to any one of the preceding claims, comprising the administration of at least one microorganism, especially a probiotic microorganism, or a fraction thereof, topically, orally or parenterally, preferably topically or orally.
14. Cosmetic treatment process comprising at least one step of administering to an individual an effective amount of at least one microorganism, especially a probiotic microorganism, or a fraction thereof, the said process being intended to be performed before or after applying to the said individual at least one surface skin treatment chosen from chemical peeling treatments and laser treatments, and/or at least one invasive treatment for aesthetic purposes.
15. Cosmetic process for preparing the skin of an individual destined to undergo at least one surface skin treatment chosen from chemical peeling treatments and laser treatments, and/or at least one invasive treatment for aesthetic purposes, comprising at least the administration to the said individual of an effective amount of at least one microorganism, especially a probiotic microorganism, or a fraction thereof.
16. Cosmetic process for soothing the skin of an individual who has undergone at least one surface skin treatment chosen from chemical peeling treatments and laser treatments, and/or at least one invasive treatment for aesthetic purposes, comprising at least the administration to the said individual of an effective amount of at least one microorganism, especially a probiotic microorganism, or a fraction thereof.
17. Process according to the preceding claim, in which the individual has impaired skin as a result of the said treatment for aesthetic purposes, and especially impaired skin chosen from pruriginous skin, erythematous skin, squamous skin, oedematous skin and cicatricial skin, or skin with dyschromia.
18. Process according to any one of claims 14 to 17, characterized in that the microorganism, especially the probiotic microorganism, or a fraction thereof, is as defined in claims 8 to 11.
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