Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
  • A61K8/97—Cosmetics 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
  • A61K8/9783—Angiosperms [Magnoliophyta]
  • A61K8/9794—Liliopsida [monocotyledons]
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q19/00—Preparations for care of the skin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q5/00—Preparations for care of the hair
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q5/00—Preparations for care of the hair
  • A61Q5/02—Preparations for cleaning the hair
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
  • A61K2800/74—Biological properties of particular ingredients

Definitions

• the present invention relates to a non-therapeutic cosmetic use of an Agave extract, to a non-therapeutic cosmetic process comprising application to the skin, scalp and / or mucous membranes of an Agave extract and to a Agave extract for preventive and / or curative use.
• the skin is a vital organ in its own right which is made up of three distinct tissues, each assuming different roles thanks to different cell types and different structures.
• This multi-layered (Malpighian) and keratinized epithelium is composed of different cells associated with numerous barrier and protective functions. The majority cells are the keratinocytes which divide in the basal layer and begin their differentiation up to the stratum corneum
• the major role of the epidermis is to provide the skin, and therefore the human body, with a first line of protection against external aggressions, such as physical, chemical, water and bacteriological aggressions.
• This protection is provided in particular by the most differentiated layers and the stratum corneum known for its hydrophobic properties and its compact and waterproof appearance.
• Good differentiation and therefore good flaking are essential for a smooth, homogeneous and regular surface. All of these mechanisms depend directly on the proliferative capacities of keratinocytes. However, external stresses and age slow down this process which can then become longer and more irregular. The scaling becoming irregular and / or anarchic, smoothing defects and homogeneity of the skin surface settle.
• the dermis is a connective tissue invested mainly with fibroblasts and matrix proteins giving the skin its known qualities of compressibility and elasticity. Changes in its texture and composition are largely responsible for the changes in the skin that occur during aging. The relief and the quality of the stratum corneum are, moreover, directly conditioned by the quality and density of the dermis which underlies it.
• other cells and structures are also intercalated, such as an important circulatory and nutritive network, consisting of blood vessels and lymphatic capillaries, as well as the epidermal appendages: hair, hairs, nails, pilosebaceous glands and sweat glands, which arise in the deep dermis.
• hypodermis located deep and consisting mainly of fatty lobules (adipocytes), provides a primary support function, mechanical and thermal protection and also plays a role in storing energy reserves that can be quickly mobilized for all biological needs, such as for example cell renewal, body defense or muscle contraction.
• adipocytes fatty lobules
• the skin is the largest organ in the human body and represents 1.6 to 1.8 m 2 in an adult. It acts as a barrier against pathogens and environmental aggressors. It's about in fact of a complex ecosystem which shelters a large variety of microorganisms located on the surface of the skin (called cutaneous microbiota), in the sweat and sebaceous glands but also in the deep dermis and the hypodermis. There is thus the formation of complex interactions with the host and the different communities, influencing the health of the host's skin.
• the skin microbiota is made up of approximately 1 million germs per cm 2 and is thus made up of several hundred distinct species among which bacteria, fungi, parasites and viruses (Chen YE, Tsao H., The skin microbiome : current perspectives and future challenges, J Am Acad Dermatol, 69 (1): 143-55, 2013 ([1]); Kong HH, Segre JA., Skin microbiome: looking back to move forward, J Invest Dermatol, 132: 933-9, 2012 ([2]); Bouslimani A, Porto C, Rath CM et al., Molecular cartography of the human skin surface in 3D, Proc Natl Acad Sci USA; 112: E2120-9, 2015 ([3] )).
• the diversity of the microbiota is important between the different regions of the skin of the human body, and the scalp is no exception.
• the scalp ecosystem is home to a well-characterized microbiota. It is mainly composed of Staphylococcus spp, Cutibacterium spp and Malassezia spp (McGinley KJ, Leyden JJ, Marples RR, Kligman AM. Quantitative microbiology of the scalp in non-dandruff, dandruff, and seborrheic dermatitis. J Invest Dermatol. 1975 Jun ; 64 (6): 401-5 ([4]); Sally Grimshaw, Adrian Smith, David Taylor, Philip Helme. The human scalp microbiome: Application of next generation sequencing of microbial communities. JAAD. April 2012, Volume 66, Issue 4, Supplement 1, Page AB62 ([5])).
• Dandruff is a major problem for a very large part of the population, yet there has been a long-recognized link between dandruff and the yeast Malassezia. Indeed, in the same way as stress, the winter period, an excess of sebum or a lack of hydration, the proliferation of the latter on the skin or hair follicles is involved in the appearance of dander or dandruff.
• the yeasts of the Malassezia spp type represent approximately 46% of the microbiota of a healthy scalp, this proportion increases to 74% in the case of the presence of dandruff.
• the role of the yeasts Malassezia spp, in particular M. globosa and M. restricta, in this phenomenon has been described for many years (Dawson TL Jr. Malassezia globosa and restricta: breakthrough understanding of the etiology and treatment of dandruff and seborrheic dermatitis through whole -genome analysis. J Investig Dermatol Symp Proc. 2007 Dec; 12 (2): 15-9. Review ([6])). Mr. restricta would be represented at approximately 73% while Mr. globosa would be represented at 17%.
• Malassezia which is the most abundant yeast on the skin (50-80%), especially on oily areas of the skin, is lipophilic.
• the lipase it has allows it to produce fatty acids like oleic acid which could alter the permeability of the skin barrier, leading to inflammation and irritation (Dawson Jr TL, ([6])) .
• dandruff states are associated with skin inflammation and an alteration of the barrier function of the epidermis, responsible for the itching sensations inducing scratching and therefore strengthening the dandruff condition.
• There would be induction of an innate immune response probably mediated by an overexpression of Toll-like receptors of the TLR2 type (Ashbee HR. Update on the genus Malassezia.
• the inventors are the very first to use Agave extracts which precisely enable the above-mentioned needs to be met effectively.
• an extract of Agave tequilana has an action of strengthening the barrier function of the skin, scalp and / or mucous membranes.
• the Applicant has indeed demonstrated, after extensive research, that the use of the extract makes it possible to modify the distribution of the microbiota on the skin, the scalp and / or the mucous membranes, while retaining their concentration, making them the compounds of choice for nourishing and / or hydrating the skin, scalp and / or mucous membranes, while respecting the skin microbiota.
• a first object of the invention relates to the non-therapeutic cosmetic use of an Agave extract to strengthen the barrier function of the skin, scalp and / or mucous membranes.
• “Reinforcement of the skin barrier function” is understood, within the meaning of the present invention, to restore or maintain a normal level of in / out exchanges (water loss) and out / in (penetration of agents or hydrophilic microorganisms) of the skin, scalp and / or mucous membranes.
• strengthening the barrier function of the skin, scalp and / or mucous membranes makes it possible to prevent their degradation and / or improve their appearance.
• the improvement of the barrier function may imply, or be due, directly or indirectly, to the increase in the synthesis of the proteins involved in differentiation. epidermal, for example keratin 10, involucrine or loricrin.
• the extract of Agave reinforces the barrier function while being able to modify the distribution of microorganisms on the surface of the skin, scalp and / or mucous membranes, by playing in particular on the density of certain microorganisms, without however have a harmful effect on the microbiota as independently confirmed via counts of microorganisms.
• the microorganisms whose density and / or distribution is modified by application of the extract is at least one microorganism chosen from the group comprising Cutibacterium acnes, Malassezia restricta, Staphylococcus epidermidis and Malassezia sp.
• the invention means the cosmetic use of the extract to nourish and / or moisturize the skin, scalp and / or mucous membranes.
• the invention also includes the cosmetic use of the extract to modify the distribution of the microbiota on the skin, scalp and / or mucous membranes.
• the microbiota concerned comprises at least one microorganism chosen from Cutibacterium acnes, Malassezia restricta, Staphylococcus epidermidis and Malassezia sp.
• the modification of the distribution of the microbiota can, for example, be a reduction in the quantity and / or the density and / or the surface of aggregates of at least one microorganism on the zone concerned.
• the biofilm is not reduced in the area concerned, despite the modification of the distribution of the microbiota.
• Agave extract is understood to mean, within the meaning of the present invention, any Agave extract making it possible to obtain at least one of the effects mentioned above. It can be an extract of Agave tequilana, Agave americana or Agave attenuata. Preferably, it may be an extract of Agave tequilana.
• the agave is a monocotyledonous plant, currently classified in the family of Agavaceae. The most common species are Agave tequilana, Agave americana and Agave attenuata. The agave is endemic on the American continent and is present from the south of Canada to the North of South America and the Caribbean islands, in particular in Mexico and in all of Central America (Maria de la Soledad ALONSO GUTIÉRREZ, thesis, "Valorization of the bagasse of Agave tequilana W. cv azul: characterization, study of the digestibility and fermentation of sugars ”, 2005 ([9])).
• Agaves have an underground part in the shape of a rhizome, and an aerial part with long stems and large fibrous leaves, arranged in the shape of a rosette and which end in a thorn.
• the flowers are found at the end of the stem and are yellow-green in color (ALONSO GUTIÉRREZ ([10])).
• Agaves are known to be sources of complex sugars such as inulins.
• Inulin is a reserve polysaccharide found in plants of the Arteraceae family, in particular in the bulbs and roots of dahlias, Jerusalem artichokes, artichokes, dandelions and chicory, the latter being the most widely used source industrially. .
• Agave inulins are carbohydrate stores of the fructan type (also called fructans). Polyfructosans were extracted from Agave tequilana Weber var.
• the Agave extract can comprise fructo-oligosaccharides having a degree of polymerization less than or equal to 10 and / or inulins having a degree of polymerization greater than 10.
• the fructo-oligosaccharides can, for example, have a degree of polymerization of from 3 to 10.
• the inulins can have a degree of polymerization strictly greater than 10, for example ranging from 10 to 60, or for example from 10 to 29.
• the Agave extract can comprise or consist only of fructo-oligosaccharides having a degree of polymerization less than or equal to 10.
• the Agave extract can comprise or consist only of inulins having a higher degree of polymerization to 10.
• the fructo-oligosaccharide to inulin ratio can be understood from 100/0 to 0/100, the limits 0/100 and 100/0 being possibly not included. The ratio can for example be 75/25, or 25/75, or 50/50.
• Agave extract can be obtained by extracting carbohydrates from bagasse, clarifying the raw liquor obtained after extraction and then separating to obtain a fraction of fructo-oligosaccharides having a lower degree of polymerization or equal to 10, and / or a fraction of inulin having a degree of polymerization greater than 10. It is understood that the fructo-oligosaccharides and the inulin are therefore natural, that is to say unmodified chemically.
• An extract of Agave tequilana can be a commercial extract, for example the product Metlos ® (NEKUTLI), characterized by fructo-oligosaccharides having a degree of polymerization less than or equal to 10, and / or the product Metlin ® (NEKUTLI) characterized by real inulins having a degree of polymerization greater than 10. It can be a mixture of Metlos ® and Metlin ®, whose ratio may be equal for example to 75/25, or 25/75, or at 50/50. In the context of the invention, any mixture of fructo-oligosaccharides and inulins as defined above is considered to be an extract of Agave within the meaning of the present invention.
• the Agave extract can be applied to the skin, scalp or mucous membranes in the form of a cosmetic or dermatological composition, comprising the Agave extract as described above.
• cosmetic composition is understood to mean, in the present invention, any composition for cosmetic, ie aesthetic purposes, a composition which can be brought into contact with the surface parts of the human body, for example the epidermis, the hair systems and capillaries.
• a cosmetic composition makes it possible, exclusively or mainly, to protect them, perfume, maintain them in good condition, modify their appearance or correct surface cosmetic defects.
• “dermatological composition” means any composition for dermatological purposes, that is to say a composition which can be brought into contact with the superficial parts of the human body, for a treatment of the skin, in particular of the scalp, and integuments, such as hair or body hair.
• composition may comprise any cosmetically or dermatologically acceptable vehicle, suitable for use in contact with human and animal skin cells, in particular epidermal cells, without toxicity, irritation, undue and similar allergic response, and proportionate to a ratio reasonable benefit / risk.
• the cosmetically acceptable vehicle can for example be chosen from water, glycerin, aloe vera gel, an aqueous plant extract, surfactants of natural origin, this list not being limiting.
• the cosmetic or dermatological composition as defined above can be obtained by any suitable process known to those skilled in the art for the manufacture of a cosmetic composition. It may for example be a mixture of an agave extract as defined above, and a cosmetically and / or dermatologically acceptable vehicle. It may alternatively be, for example, a method comprising a step of incorporating an internal phase into an external phase by means of an emulsifier, for example a rotor-type turbine. stator. It may also be, for example, a process using the phase inversion temperature (TIP), this process being conventionally used by those skilled in the art to obtain oil-in-water emulsions in which the dispersed droplets are particularly fines, for example with a diameter of 0.1 to 1 ⁇ m.
• TIP phase inversion temperature
• the cosmetic or dermatological composition may comprise from 0.05 to 5% by weight of Agave extracts relative to the total weight of the composition, for example from 0.1 to 5%, from 0.1 to 1%, from 0.25 to 1% or 0.25 to 0.5%.
• the cosmetic or dermatological composition can be in any form suitable for cosmetic or dermatological application.
• the composition is a composition for topical use, rinsed or leave-in.
• the cosmetic or dermatological composition can for example be in a form chosen from the group comprising an aqueous or hydroalcoholic gel, an aqueous or hydroalcoholic cream and an aqueous or hydroalcoholic lotion.
• these formulations which can be used for the implementation of the present invention are known in the prior art by formulators. In these composition examples, it suffices to add extracts of Agave of the present invention to obtain a composition in accordance with the present invention.
• the composition can be in a form chosen from a shampoo, an ointment, a cream, an oil, a milk, an ointment, a powder, a solution, a gel, a serum, a balm, a butter, a lotion, a suspension, a soap or an emulsion, this form being able to be rinsed or not rinsed.
• the extract of the present invention can be used in a cosmetic or dermatological composition alone or in combination with other He
• cosmetically or dermatologically active or inactive substances or ingredients are those that do not act cosmetically or dermatologically.
• Inactive substances or ingredients are those that do not act cosmetically or dermatologically. These are the elements of the composition which make it possible in particular to accompany the extract, to constitute a particular formulation, to keep the extract active over time, this list not being limiting. In other words, it can be any basic product which can be found in conventional cosmetic or dermatological compositions.
• the active substances or ingredients are those which in the intended cosmetic or dermatological application have an aesthetic and / or medical action.
• the Agave extract of the present invention can be the only active substance or ingredient in a composition, or it can be combined with other active substances or ingredients in a cosmetic or dermatological composition.
• Another subject of the invention relates to a non-therapeutic, cosmetic or dermatological treatment process for strengthening the barrier function of the skin, scalp and / or mucous membranes, comprising an application to the skin, the scalp and / or the mucous membranes of an Agave extract as defined above.
• the use means a non-therapeutic use, for example for the treatment of healthy skin, scalp and mucous membranes, that is to say in particular not presenting a pathological state and / or for a strictly aesthetic use, to the exclusion of any therapeutic use.
• the cosmetic and aesthetic use of the invention is not associated with an inevitable therapeutic effect.
• any cosmetic use and any cosmetic method according to the invention are non-therapeutic cosmetic uses and non-therapeutic cosmetic methods, respectively, which are not intended to treat a pathology.
• Another subject of the invention relates to an Agave extract for its use in the treatment and / or prevention of a more or less recurrent inflammation of the skin, scalp and / or mucous membranes, linked to the more or less excessive presence of at least one microorganism chosen from Cutibacterium acnes, Malassezia restricta, Staphylococcus epidermidis and Malassezia sp. Inflammation may include a skin manifestation chosen from itching, irritation and redness.
• the Applicant has in fact surprisingly found that the expression of TNF-alpha, increased in the event of contact, is very significantly inhibited after the application, on the skin concerned, of the Agave extract.
• this may indicate a reduction in the inflammation induced by the microorganisms, if any.
• FIG. 1 represents the histo-morphology (sectional view) at 72 hours of the reconstructed human epidermis (EHR) colonized with Cutibacterium acnes and Malassezia restricta and treated or not with Agave extracts, as described in Example 2.
• EHR human epidermis
• FIG. 2 represents the 72 h ultrastructural analysis of EHRs colonized with Cutibacterium acnes and Malassezia restricta and treated or not with Agave extracts are shown in FIG. 2.
• A Untreated EHR.
• B EHR treated with the formula with Agave extracts.
• C EHR treated with the formula without Agave extracts.
• the raw material used for the production of fructooligosaccharides with a degree of polymerization less than or equal to 10 (commercial product Metlos ® ) and inulins with a degree of polymerization greater than 10 (commercial product Metlin ® ) is the organic blue agave harvested in the high plateaus of the state of Jalisco. After 5 to 7 years of carefully controlled growth, the Agave has the maximum amount of fructans, and is therefore ready for processing.
• the agave is received fresh and washed on arrival to remove as much foreign matter as possible.
• the agave is then ground in three stages to go from 40 to 100 kg of agave kernel to a pulpy bagasse, ready to be transformed into extracting the carbohydrates.
• Example 2 Effect of the Agave Extracts Obtained in Example 1 on the Skin / Microbiota Communication
• EHR human epidermis
• Episkin® reconstructed human epidermis
• This model reproduces the morphology of the epidermis.
• the EHRs are transferred to 6-well plates previously filled with culture medium (1 ml / well) and then they are incubated at 37 ° C. with 5% CO 2, saturated in humidity, for 3 h before starting. the study itself.
• the microorganisms of Cutibacterium acnes and Malassezia restricta are inoculated on the surface of the epidermis at the rate of approximately 10 7 CFU / cm 2 and 10 5 CFU / cm 2 .
• Oil Food grade olive is added to crops especially for Malassezia restricta.
• a serum-type formula containing or not containing 0.5% Agave extracts is applied to the surface of the epidermis / microorganism model, then this operation is repeated every 24 hours for 72 hours. From the inoculation of the epidermis, the model is maintained at 32 ° C, with 5% CO2, saturated with humidity.
• a rating is made from 0 to 4 (1: 0 or very weak marking, 2: diffuse marking, 3: localized marking, 4: strong marking).
• the 3 differentiation markers show that Agave extracts increase the intensity of expression of the latter, which induces an improvement in the barrier function and better protection.
• the results of the 72 h ultrastructural analysis of EHRs colonized with Cutibacterium acnes and Malassezia restricta and treated or not with Agave extracts are shown in FIG. 2.
• Untreated EHR very clearly shows significant aggregates of microorganisms and in particular Malassezia restricta which is more visible because it is larger than Cutibacterium acnes (approximately 4-8 pm vs 2pm). Malassezia restricta is located on the surface while some Cutibacterium acnes cells are visible on the surface but most of it covers the epidermis in the form of biofilm.
• Treatment with the formula containing Agave extracts shows a strong reduction in surface aggregates without reducing the biofilm.
• Treatment with the formula without Agave extracts again shows the presence of aggregates even if their density remains less consistent than with untreated EHR.
• the Agave extract reinforces the barrier function and is capable of modifying the distribution of microorganisms on the surface of EHRs by playing in particular on the density of Malassezia restricta, without having any harmful effect on the microbiota as confirmed independently via counts of microorganisms.
• Example 3 Effect of a Serum Containing Agave Extracts Obtained in Example 1 on Skin Inflammation
• EHR episkin® human epidermis
• This model reproduces the morphology of the epidermis.
• the EHRs are transferred to 6-well plates previously filled with culture medium (1 ml / well) and then they are incubated at 37 ° C with 5% CO2, saturated with humidity, for 3 h before starting the study itself. After this period and according to the conditions, the microorganisms of
• Cutibacterium acnes and Malassezia restricta are inoculated on the surface epidermis at a rate of approximately 10 7 CFU / cm 2 and 10 5 CFU / cm 2 .
• Food grade olive oil is added to the crops especially for Malassezia restricta.
• a serum type formula containing or not containing 0.5% Agave extracts is applied to the surface of the epidermis / microorganism model, then this operation is repeated every 24 hours for 72 hours. From the inoculation of the epidermis, the model is maintained at 32 ° C, with 5% CO2, saturated with humidity. After 72 hours of coculture and application of Agave extracts in formula, the gene expression by qRT-PCR of the TNF-a markers was measured.
• Table II shows the quantifications of the expression of TNF-alpha at 72 h of the EHRs colonized with Cutibacterium acnes and Malassezia restricta and not treated or treated with the formula with the extracts of Agave.
• TNF-alpha The synthesis of TNF-alpha is increased in case of infection, this is what we measure in the model not treated with a formula.
• the formula When the formula is applied with Agave extracts, there is a very substantial inhibition of its expression, indicating a reduction in inflammation induced by microorganisms.
• Example 5 Formulation of Agave Extracts in a Day Care
• Example 6 Formulation of agave extracts in a night treatment.
• Example 7 Formulation of an Agave Extract in a Hair Care Serum
• Example 8 Formulation of an Agave Extract in a Shampoo

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