FR2897778A1 - Preparing active ingredient useful e.g. to improve skin from fatty and/or acne condition comprises solubilizing meadowsweet powder in hydroalcoholic mixture, eliminating polyphenol part, separating soluble/insoluble phases, purifying - Google Patents
Preparing active ingredient useful e.g. to improve skin from fatty and/or acne condition comprises solubilizing meadowsweet powder in hydroalcoholic mixture, eliminating polyphenol part, separating soluble/insoluble phases, purifying Download PDFInfo
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- FR2897778A1 FR2897778A1 FR0650690A FR0650690A FR2897778A1 FR 2897778 A1 FR2897778 A1 FR 2897778A1 FR 0650690 A FR0650690 A FR 0650690A FR 0650690 A FR0650690 A FR 0650690A FR 2897778 A1 FR2897778 A1 FR 2897778A1
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- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
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- XUGNVMKQXJXZCD-UHFFFAOYSA-N isopropyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)C XUGNVMKQXJXZCD-UHFFFAOYSA-N 0.000 description 1
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- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
-
- 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]
- A61K8/9789—Magnoliopsida [dicotyledons]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
- A61Q17/005—Antimicrobial preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/008—Preparations for oily skin
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Engineering & Computer Science (AREA)
- Botany (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medical Informatics (AREA)
- Alternative & Traditional Medicine (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Birds (AREA)
- Dermatology (AREA)
- Cosmetics (AREA)
Abstract
Description
PROCEDE D'OBTENTION D'UN ACTIF COSMETIQUE POUR AMELIORER L'ETAT DES PEAUXPROCESS FOR OBTAINING A COSMETIC ACTIVE TO IMPROVE THE CONDITION OF SKINS
A TENDANCE GRASSE ET/OU ACNEIQUE, PRINCIPE ACTIF OBTENU ET COMPOSITIONS ASSOCIEES A FATTY AND / OR ACNEIC TRENDS, ACTIVE INGREDIENTS OBTAINED AND COMPOSITIONS THEREOF
La présente invention a trait à un procédé d'obtention d'un principe actif issu de Reine des prés pour améliorer l'état des peaux à tendance grasse et/ou acnéique. L'invention se rapporte également au principe actif susceptible d'être obtenu par ce procédé et aux compositions cosmétiques associées. The present invention relates to a method for obtaining an active ingredient derived from Meadowsweet to improve the condition of oily and / or acne-prone skin. The invention also relates to the active ingredient that can be obtained by this method and to the associated cosmetic compositions.
L'acné est un problème de peau très fréquent qui se trouve particulièrement accentué entre 12 et 25 ans. Il se manifeste notamment par une peau grasse accompagnée d'imperfections difficiles à masquer et à assumer. Ce caractère inesthétique a généralement des répercussions psychologiques, et beaucoup de gens souhaitent vivement remédier à cette situation d'inconfort. Acne is a very common skin problem that is particularly accentuated between 12 and 25 years of age. It is particularly manifested by oily skin with imperfections difficult to mask and assume. This unsightly nature usually has psychological implications, and many people are keen to remedy this discomfort.
L'apparition des manifestations cutanées acnéiques est notamment liée à un développement bactérien à la surface de la peau. C'est pourquoi le principe actif selon la présente invention se propose d'améliorer l'état des peaux grasses et/ou acnéiques en prévenant la prolifération des bactéries à la surface de la peau. The appearance of cutaneous acne manifestations is particularly related to a bacterial development on the surface of the skin. This is why the active ingredient according to the present invention proposes to improve the state of oily and / or acne skin by preventing the proliferation of bacteria on the surface of the skin.
La peau est naturellement colonisée par une microflore dont l'équilibre assure un rôle de barrière en limitant l'invasion et la croissance des bactéries pathogènes à la surface cutanée. Un changement de l'environnement cutané, un manque temporaire d'hygiène, un changement de statut hormonal peut bouleverser cet équilibre permettant ainsi une contamination de la couche cornée par des germes pathogènes. The skin is naturally colonized by a microflora whose balance provides a barrier by limiting the invasion and growth of pathogenic bacteria on the skin surface. A change in the skin environment, a temporary lack of hygiene, a change in hormonal status can upset this balance thus allowing a contamination of the stratum corneum by pathogenic germs.
La cause initiale de l'acné est l'obstruction du canal pilo-sébacé par kératinisation anormale des parois du follicule et par hypersécrétion de sébum. Cette occlusion entraîne la formation d'une lésion rétentionnelle sous forme de comédon ouvert, dit point noir, ou de microkyste fermé, dit point blanc. Les germes pathogènes de la peau, tels que Propionibactérium acnes (P. acnes) et Staphylococcus aureus (S. aureus), sont alors dans des conditions idéales pour proliférer et entraîner une réaction inflammatoire à l'intérieur du follicule se traduisant par l'apparition de papules, pustules ou nodules. Pour éviter les désordres cutanés acnéiques et limiter les complications, il est 10 important d'agir directement sur les bactéries pathogènes responsables des processus inflammatoires. De fait, la présente invention a pour objectif de lutter directement contre les bactéries présentes à la surface des peaux à tendance acnéique en réduisant la prolifération de P. acnes et en inhibant la croissance de S. aureus. 15 Pour lutter contre les infections microbiennes, la peau est équipée d'un système de défense naturelle. Certaines cellules épithéliales, notamment les kératinocytes, produisent et sécrètent des peptides anti-microbiens naturels, en particulier les cathélicidines, qui limitent la prolifération des germes pathogènes. Les cathélicidines sont capables de désorganiser la membrane bactérienne en la 20 perméabilisant et peuvent également induire une réponse immunitaire indirecte grâce à leur propriété chimiotactique vis-à-vis des cellules immunitaires. Dans le cas des peaux à tendance acnéique, les défenses naturelles sont souvent déréglées ou dépassées. Il est donc nécessaire de les stimuler pour lutter contre les germes pathogènes cutanés et limiter les réactions inflammatoires impliquées 25 dans l'apparition des imperfections de la peau liées à l'acné. Ainsi, la présente invention a également pour objectif de favoriser le retour de l'écosystème cutané pour lutter contre la prolifération des bactéries présentes à la surface des peaux à tendance grasse et/ou acnéique en stimulant les fonctions naturelles de défense de la peau. En particulier, la présente invention se propose d'augmenter la synthèse des cathélicidines, anti-microbiens naturels impliqués dans la réponse immunitaire innée de la peau. Un autre facteur important impliqué dans l'acné est la sécrétion sébacée. The initial cause of acne is obstruction of the pilosebaceous canal by abnormal keratinization of the follicle walls and hypersecretion of sebum. This occlusion leads to the formation of a retentive lesion in the form of an open comedo, called a black dot, or a closed microcyst, called a white dot. The pathogens of the skin, such as Propionibacterium acnes (P. acnes) and Staphylococcus aureus (S. aureus), are then under ideal conditions to proliferate and cause an inflammatory reaction inside the follicle resulting in the appearance papules, pustules or nodules. To avoid acne skin disorders and limit complications, it is important to act directly on the pathogenic bacteria responsible for the inflammatory processes. In fact, the present invention aims to fight directly against bacteria present on the surface of acne-prone skin by reducing the proliferation of P. acnes and inhibiting the growth of S. aureus. To fight against microbial infections, the skin is equipped with a natural defense system. Some epithelial cells, including keratinocytes, produce and secrete natural anti-microbial peptides, particularly cathelicidines, which limit the proliferation of pathogens. Cathelicidines are capable of disrupting the bacterial membrane by permeabilizing it and may also induce an indirect immune response by virtue of their chemotactic property with respect to immune cells. In the case of acne-prone skin, natural defenses are often out of order or out of date. It is therefore necessary to stimulate them to fight against skin pathogens and limit the inflammatory reactions involved in the appearance of acne-related skin blemishes. Thus, the present invention also aims to promote the return of the skin ecosystem to fight against the proliferation of bacteria on the surface of oily and / or acne-prone skin by stimulating the natural defense functions of the skin. In particular, the present invention proposes to increase the synthesis of natural anti-microbial cathelicidines involved in the innate immune response of the skin. Another important factor involved in acne is sebaceous secretion.
Le sébum résulte de la sécrétion holocrine des glandes sébacées et se forme par la désintégration de leurs cellules glandulaires à contenu lipidique. L'hyper-séborrhée favorise la prolifération bactérienne cutanée impliquée dans l'apparition des imperfections de l'acné. La sécrétion excessive de sébum se manifeste par une peau brillante, irritée et une sensation d'inconfort typique des peaux grasses et/ou acnéiques. Aussi, la présente l'invention se propose de limiter les conséquences de l'hyperséborrhée sur les peaux à tendance grasse et/ou acnéique en régulant la sécrétion de sébum à la surface de la peau. Le principe actif selon la présente invention améliore donc l'état des peaux à 15 tendance grasse et/ou acnéique en limitant la prolifération de bactéries pathogènes à la surface de la peau par : - stimulation des fonctions naturelles de défenses de la peau, en particulier par augmentation de la synthèse des cathélicidines, - inhibition de la prolifération des germes directement impliqués dans 20 l'apparition des désordres cutanés, notamment P. acnes et S. aureus, et - diminution de la sécrétion de sébum à la surface de la peau. Ainsi le principe actif selon l'invention permet d'améliorer toutes les manifestations caractéristiques des peaux à tendance grasse et/ou acnéique. Il limite le nombre de lésions et améliore l'homogénéité du grain de la peau. 25 La présente invention est maintenant décrite en détail pour permettre de mieux appréhender les résultats obtenus regroupés en tableaux. 1/ PROCEDE D'OBTENTION DU PRINCIPE ACTIF SELON L'INVENTION : Le procédé d'obtention du principe actif selon l'invention comprend la succession des étapes suivantes : - solubilisation de poudre de Reine des prés dans un mélange hydroalcoolique constitué d'eau et de butylène glycol, - élimination sélective d'une partie des polyphénols par adsorption, - séparation des phases solubles et insolubles par centrifugation, décantation, filtration, - purification de la fraction active, - filtration, et - filtration stérilisante. 2/ CARACTERISATION DU PRINCIPE ACTIF SELON L'INVENTION : 2-1/ Matières sèches : On mesure le taux de matières sèches par passage à l'étuve à 105 C en présence de sable d'un échantillon de poids initial donné jusqu'à obtention d'un poids constant. Le taux de matières sèches est compris entre 6 et 40 g/I, plus particulièrement entre 15 et 23 g/I. 2-2/ Mesure du pH : Le pH mesuré par la méthode potentiométrique à température ambiante conduit à des valeurs comprises entre 3,5 et 6,5, plus particulièrement entre 4,5 et 5,5. 2-3/ Dosage des composés phénoliques Le dosage est réalisé par lecture de l'intensité de coloration en présence de ferricyanure de potassium, intensité détectable à 715 nm et comparée à une gamme étalon d'acide gallique. Le taux de polyphénol est compris entre 0,3 et 1,8 g/I, plus particulièrement entre 0,6 à 1 g/I. 2-4/ Caractérisation des composés phénoliques La caractérisation et la quantification des composés phénoliques du principe actif selon l'invention sont réalisées par HPLC (High Performance Liquid Chromatography). Sebum results from the holocrine secretion of the sebaceous glands and is formed by the disintegration of their glandular cells with lipid content. Hyper-seborrhea promotes cutaneous bacterial proliferation involved in the appearance of acne blemishes. The excessive secretion of sebum is manifested by a shiny, irritated skin and a sensation of discomfort typical of oily and / or acne skin. Also, the present invention proposes to limit the consequences of hyperseborrhoea on oily and / or acne-prone skin by regulating the secretion of sebum on the surface of the skin. The active ingredient according to the present invention therefore improves the condition of oily and / or acne-prone skin by limiting the proliferation of pathogenic bacteria on the surface of the skin by: - stimulating the natural functions of the skin's defenses, in particular by increasing the synthesis of the cathelicidines, - inhibition of the proliferation of the germs directly involved in the appearance of cutaneous disorders, in particular P. acnes and S. aureus, and - decrease in the secretion of sebum on the surface of the skin. Thus, the active ingredient according to the invention makes it possible to improve all the characteristic manifestations of oily and / or acne-prone skin. It limits the number of lesions and improves the homogeneity of the grain of the skin. The present invention is now described in detail to allow a better understanding of the results obtained grouped in tables. 1 / PROCESS FOR OBTAINING THE ACTIVE INGREDIENT ACCORDING TO THE INVENTION: The process for obtaining the active ingredient according to the invention comprises the following succession of steps: - solubilization of Meadowsweet powder in a hydroalcoholic mixture consisting of water and butylene glycol, - selective removal of a portion of polyphenols by adsorption, - separation of soluble and insoluble phases by centrifugation, decantation, filtration, - purification of the active fraction, - filtration, and - sterilizing filtration. 2 / CHARACTERIZATION OF THE ACTIVE INGREDIENT ACCORDING TO THE INVENTION: 2-1 / Dry matter: The rate of solids is measured by passing the oven at 105 ° C. in the presence of sand of a sample of initial weight given until obtaining of a constant weight. The solids content is between 6 and 40 g / l, more particularly between 15 and 23 g / l. 2-2 / pH measurement: The pH measured by the potentiometric method at room temperature leads to values between 3.5 and 6.5, more particularly between 4.5 and 5.5. 2-3 / Determination of phenolic compounds The assay is carried out by reading the staining intensity in the presence of potassium ferricyanide, detectable intensity at 715 nm and compared to a standard range of gallic acid. The polyphenol content is between 0.3 and 1.8 g / l, more particularly between 0.6 and 1 g / l. 2-4 / Characterization of Phenolic Compounds The characterization and quantification of the phenolic compounds of the active principle according to the invention are carried out by HPLC (High Performance Liquid Chromatography).
Le chromatogramme du principe actif selon l'invention montre la présence de composés hydroxycinnamiques, hydroxybenzoïques, de flavone et de flavonol, les proportions étant sensiblement de l'ordre des valeurs données dans le tableau suivant : Famille de polyphénols Concentration identifiée Flavonol 65% Hydroxycinnamiques 18,8% Hydroxybenzoïques 15,4% Flavone 0, 8% 2-5/ Identification de la fraction active Pour déterminer la ou les fractions actives, on utilise du polyvinylpolypyrolidone (PVPP) de façon à éliminer la totalité des polyphénols du principe actif selon l'invention. On compare ensuite la capacité d'inhibition de prolifération bactérienne de la fraction privée des polyphénols à celle du principe actif selon l'invention. Testés à la même concentration, le principe actif selon l'invention présente une activité inhibitrice de la prolifération bactérienne alors que la fraction privée des polyphénols n'a plus cette activité. Par conséquent, ce sont les composés phénoliques qui confèrent au principe 20 actif selon l'invention son activité d'inhibition de la prolifération bactérienne. 3/EVALUATION DE L'EFFET DU PRINCIPE ACTIF SELON L'INVENTION 3-1/ Evaluation de l'effet sur la synthèse des cathélicidines Cette étude a pour objectif d'évaluer l'effet du principe actif selon l'invention sur l'expression des ARNm codant pour les cathélicidines, peptides anti-microbiens synthétisés par les kératinocytes humains, essentiels pour la défense contre les infections de la peau. Elle est réalisée sur des kératinocytes humains normaux selon le protocole qui suit. A JO les cellules sont ensemencées puis incubées dans une étuve à 37 C. The chromatogram of the active principle according to the invention shows the presence of hydroxycinnamic, hydroxybenzoic, flavone and flavonol compounds, the proportions being substantially of the order of the values given in the following table: Polyphenol family Identified concentration Flavonol 65% Hydroxycinnamiques 18 , 8% Hydroxybenzoic acid 15.4% Flavone 0.8% 2-5 / Identification of the active fraction To determine the active fraction or fractions, polyvinylpolypyrrolidone (PVPP) is used so as to eliminate all the polyphenols of the active ingredient according to 'invention. The bacterial proliferation inhibition capacity of the fraction deprived of polyphenols is then compared with that of the active principle according to the invention. Tested at the same concentration, the active ingredient according to the invention has an inhibitory activity of bacterial proliferation while the private fraction of polyphenols no longer has this activity. Therefore, it is the phenolic compounds which confer on the active principle according to the invention its bacterial proliferation inhibiting activity. 3 / EVALUATION OF THE EFFECT OF THE ACTIVE PRINCIPLE ACCORDING TO INVENTION 3-1 / Evaluation of the effect on the synthesis of cathelicidines This study aims to evaluate the effect of the active principle according to the invention on the expression mRNAs encoding the anti-microbial peptides synthesized by human keratinocytes, which are essential for the defense against skin infections. It is carried out on normal human keratinocytes according to the protocol that follows. At 0, the cells are inoculated and incubated in an oven at 37 ° C.
A J1 et à J4 le milieu de culture est renouvelé. A J5, les kératinocytes sont traités avec le principe actif selon l'invention à 0,2%, 0,4% et 1,0%, puis sont de nouveau incubés à 37 C. A J6, les cellules sont récupérées et on extrait les ARN totaux qui sont reverses-transcripts. Les ADN complémentaires obtenus sont ensuite analysés par PCR (Polymerase Chain Reaction) quantitative. Les résultats obtenus, exprimés en pourcentage par rapport au témoin de référence, sont présentés dans le tableau suivant : Taux d'ARNm des cathélicidines / Témoin (%) Principe actif selon l'invention 0,2% + 12 Principe actif selon l'invention 0,4% + 55 Principe actif selon l'invention 1% + 130 On constate que le principe actif selon l'invention augmente la synthèse des ARNm des cathélicidines, cet effet étant dose-dépendant. Testé à 1% sur kératinocytes humains normaux, il augmente de 130% la synthèse des ARNm des cathélicidines. On D1 and D4 the culture medium is renewed. At D5, the keratinocytes are treated with the active principle according to the invention at 0.2%, 0.4% and 1.0%, and are then incubated again at 37 ° C. At day 6, the cells are recovered and extracted. total RNAs that are reverse-transcripts. The complementary DNAs obtained are then analyzed by quantitative PCR (Polymerase Chain Reaction). The results obtained, expressed as a percentage relative to the reference control, are presented in the following table: mRNA level of cathelicidines / control (%) active principle according to the invention 0.2% + 12 active principle according to the invention 0.4% + 55 active principle according to the invention 1% + 130 It is found that the active ingredient according to the invention increases the synthesis of mRNA of cathelicidines, this effect being dose-dependent. Tested at 1% on normal human keratinocytes, it increases by 130% the synthesis of the mRNAs of the cathelicidines.
Le principe actif selon l'invention permet donc d'augmenter la synthèse d'anti-microbiens par les kératinocytes et par conséquent la défense contre les infections de la peau. 3-2/ Evaluation de l'effet sur la prolifération bactérienne Le but de cette étude est d'évaluer l'activité antimicrobienne directe du principe actif selon l'invention. Cette étude est réalisée par mise en contact du principe actif selon l'invention avec une suspension bactérienne de Staphylococcus aureus (S. aureus) ou de Propionibacterium acnes (P. acnes). The active ingredient according to the invention therefore makes it possible to increase the synthesis of antimicrobials by keratinocytes and consequently the defense against skin infections. 3-2 / Evaluation of the effect on bacterial proliferation The purpose of this study is to evaluate the direct antimicrobial activity of the active principle according to the invention. This study is carried out by contacting the active ingredient according to the invention with a bacterial suspension of Staphylococcus aureus (S. aureus) or Propionibacterium acnes (P. acnes).
Le principe actif selon l'invention dosé à 2,5% et 5% est mis en contact avec la suspension microbienne à 10' germes/ml dans les proportions 9 volumes de principe actif pour 1 volume de suspension. L'incubation est réalisée à 30 C pendant 12 heures pour S. aureus et à 30 C en milieu anaérobie pendant 7 jours pour P. acnes. The active ingredient according to the invention, assayed at 2.5% and 5%, is brought into contact with the microbial suspension at 10 7 / ml in proportions of 9 volumes of active ingredient per 1 volume of suspension. The incubation is carried out at 30 ° C. for 12 hours for S. aureus and at 30 ° C. in an anaerobic medium for 7 days for P. acnes.
Après incubation on dénombre les germes. Les résultats obtenus sont présentés dans le tableau qui suit en pourcentage d'inhibition de la croissance du germe % d'inhibition de la /G d'inhibition de la croissance de S. aureus croissance de P. acnes Principe actif 2,5% -60,6 -58,0 Principe actif 5,0% -81,6 -92,0 Ces résultats montrent que le principe actif selon l'invention inhibe la croissance de S. aureus et de P. acnes, ces effets étant dose-dépendants. Lorsqu'il est dosé à 5% le principe actif selon l'invention inhibe de 82% la croissance de S. aureus et de 92% celle de P. acnes. After incubation we count the germs. The results obtained are presented in the following table as a percentage of inhibition of the growth of the germ% inhibition of the growth inhibition of S. aureus growth of P. acnes 2.5% active ingredient - 60.6 -58.0 active ingredient 5.0% -81.6 -92.0 These results show that the active ingredient according to the invention inhibits the growth of S. aureus and P. acnes, these effects being dependent. When dosed at 5%, the active ingredient according to the invention inhibits the growth of S. aureus by 82% and that of P. acnes by 92%.
Le principe actif selon l'invention présente donc une effet anti-microbien direct. 3-3/ Etude des propriétés anti-séborrhéiques Le but de cette étude est de quantifier in vivo l'efficacité anti-séborrhée du principe actif selon l'invention formulé à 4% en émulsion contre placebo. L'étude est réalisée sur des volontaires sains d'âge compris entre 21 et 64 ans, avec un taux de sébum supérieur à 190. Elle consiste à la fois à mesurer l'indice lipidique et à visualiser et quantifier les lipides épidermiques, avant et après 28 jours d'applications biquotidiennes du principe actif selon l'invention et du placebo. La mesure du sébum est réalisée à l'aide d'un Sébumètre, dispositif qui permet une mesure directe de la sécrétion sébacée en pg de sébum / cm2 de peau. La visualisation et la quantification du sébum sont réalisées au moyen d'un patch (Sebutape), constitué d'une bandelette particulièrement sensible aux sécrétions sébacées. La bandelette est ensuite analysée à l'aide d'un logiciel d'analyse d'images pour apprécier le nombre et l'importance des taches dont la surface est proportionnelle à la quantité de lipides excrétés. Le protocole opératoire est décrit ci-dessous. The active ingredient according to the invention thus has a direct anti-microbial effect. 3-3 / Study of anti-seborrhoeic properties The purpose of this study is to quantify in vivo the anti-seborrhea efficacy of the active ingredient according to the invention formulated at 4% emulsion against placebo. The study is carried out on healthy volunteers between 21 and 64 years old, with a sebum level greater than 190. It consists of both measuring the lipid index and visualizing and quantifying the epidermal lipids, before and after after 28 days of twice-daily application of the active ingredient according to the invention and placebo. Measurement of sebum is performed using a Sebumeter, device that allows a direct measurement of sebaceous secretion in pg of sebum / cm2 of skin. Visualization and quantification of sebum are performed using a patch (Sebutape), consisting of a strip particularly sensitive to sebaceous secretions. The strip is then analyzed using an image analysis software to assess the number and importance of stains whose surface is proportional to the amount of lipids excreted. The operating protocol is described below.
A JO, on détermine deux zones cutanées symétriques au niveau du front, une destinée à être traitée par le principe actif selon l'invention, l'autre par le placebo. Sur chacune de ces zones on effectue trois mesures de l'indice lipidique puis on applique un patch (Sebutape) pendant 30 minutes sur la peau préalablement dégraissée à l'alcool. At OJ, two symmetrical cutaneous zones are determined at the forehead, one to be treated with the active ingredient according to the invention, the other by the placebo. On each of these zones, three measurements of the lipid index are carried out and then a patch (Sebutape) is applied for 30 minutes on the skin previously degreased with alcohol.
Entre JO et J27, le principe actif selon l'invention et le placebo sont appliqués bi quotidiennement. Between OJ and J27, the active ingredient according to the invention and the placebo are applied bi daily.
A J28, on effectue à nouveau sur chacune des zones trois mesures de l'indice lipidique et on applique un patch Sebutape pendant 30 minutes sur la peau préalablement dégraissée à l'alcool. At day 28, three measurements of the lipid index were again performed on each of the zones and a Sebutape patch was applied for 30 minutes to the skin previously defatted with alcohol.
a - Mesure de l'indice lipidique Les résultats en pg de sébum / cm2 de peau relatifs à la sébumétrie sont présentés dans le tableau qui suit : JO J28 Placebo 254 195 Principe actif selon l'invention 4% 263 179 Variation / Placebo (%) -12 On constate que le principe actif selon l'invention formulé à 4% en 10 émulsion, diminue de 12% l'indice lipidique après 28 jours d'applications biquotidiennes. b - Visualisation et quantification des lipides épidermiques Les paramètres étudiés sont le nombre de spots lipidiques par cm2 de peau et la surface totale occupée par les spots lipidiques. 15 Les résultats sont présentés dans le tableau suivant : Variation / Placebo (%) Nombre de spots / cm2 -10 Surface totale occupée -12 Ces résultats montrent que le principe actif selon l'invention formulé à 4% en émulsion, après 28 jours d'applications biquotidiennes, entraîne une diminution du nombre de spots de 10% et de la surface totale occupée de 12%. Le principe actif selon l'invention diminue donc la sécrétion de sébum au niveau de la peau. 3-4/ Effet astringent Cette étude a pour objectif de visualiser in vivo l'effet astringent du principe actif selon l'invention formulé à 4% en émulsion. L'étude est réalisée sur des volontaires sains d'âge compris entre 21 et 40 10 ans par visualisation des pores sur les ailes du nez à l'aide d'une caméra noir et blanc et d'un éclairage UVA. A t0, on récupère les images des pores au niveau de 2 zones sur les ailes du nez. On applique ensuite 15 pl du principe actif selon l'invention ou du placebo. 15 Après 15 minutes on récupère à nouveau les images des pores au niveau des deux zones. On étudie le diamètre de trois pores choisis de manière aléatoire sur chaque zone. Les résultats sur le diamètre des pores en millimètres sont présentés dans 20 le tableau suivant : TO T15 Placebo 0,35 0,35 Principe actif selon l'invention 4% 0,38 0,36 Variation / Placebo (%) -5 Ces résultats montrent qu'après une application unique et en comparaison au placebo, le principe actif selon l'invention formulé à 4% dans une émulsion diminue le diamètre des pores de la peau de 5%. 3-5/ Evaluation dermatologique de l'effet anti-acnéique Cette étude a pour objectif d'évaluer in vivo l'effet du principe actif selon l'invention formulé à 4% en émulsion contre placebo sur les peaux à tendance acnéique. Elle est réalisée sur 22 volontaires sains, d'âge compris entre 23 et 32 ans. a - Measurement of the lipid index The results in pg of sebum / cm 2 of skin relative to the sebumetry are presented in the following table: OJ J28 Placebo 254 195 Active principle according to the invention 4% 263 179 Variation / placebo (% It is found that the active ingredient according to the invention formulated at 4% emulsion reduces the lipid index by 12% after 28 days of twice-daily application. b - Visualization and quantification of epidermal lipids The parameters studied are the number of lipid spots per cm2 of skin and the total area occupied by the lipid spots. The results are presented in the following table: Variation / Placebo (%) Number of spots / cm 2 -10 Total surface occupied -12 These results show that the active principle according to the invention formulated at 4% in emulsion, after 28 days. twice-daily applications reduces the number of spots by 10% and the total area occupied by 12%. The active ingredient according to the invention therefore decreases the secretion of sebum at the level of the skin. 3-4 / Astringent effect This study aims to visualize in vivo the astringent effect of the active ingredient according to the invention formulated at 4% emulsion. The study is carried out on healthy volunteers between 21 and 40 years old by visualization of the pores on the wings of the nose using a black and white camera and a UVA lighting. At t0, the images of the pores are recovered at 2 zones on the wings of the nose. 15 μl of the active ingredient according to the invention or placebo are then applied. After 15 minutes the pore images are recovered again at the two zones. The diameter of three pores chosen randomly on each zone is studied. The results on the pore diameter in millimeters are presented in the following table: TO T15 Placebo 0.35 0.35 Active ingredient according to the invention 4% 0.38 0.36 Variation / placebo (%) -5 These results show that after a single application and in comparison with placebo, the active ingredient according to the invention formulated at 4% in an emulsion reduces the pore diameter of the skin by 5%. 3-5 / Dermatological evaluation of the anti-acne effect This study aims to evaluate in vivo the effect of the active ingredient according to the invention formulated at 4% emulsion against placebo on acne-prone skin. It is performed on 22 healthy volunteers, between 23 and 32 years old.
L'étude, qui consiste à effectuer une évaluation dermatologique et à prendre des photographies de haute résolution pour compter les lésions, est réalisée selon le protocole opératoire qui suit. A JO, on effectue une évaluation dermatologique et on prend des photographies haute résolution sur chacun des hémi-visages des volontaires. The study, which consists of performing a dermatological evaluation and taking high-resolution photographs to count the lesions, is performed according to the operating protocol that follows. At OJ, a dermatological evaluation is performed and high-resolution photographs are taken of each of the volunteers' hemispheres.
Entre JO et J27, le principe actif selon l'invention et le placebo sont appliqués deux fois par jour. A J28, on réalise à nouveau une évaluation dermatologique et on prend des photographies haute résolution sur chacun des hémi-visages des volontaires. a - Evaluation dermatologique L'évaluation est basée sur un examen clinique réalisé sur les deux hémivisages. Les points étudiés sont : - Al : peau à tendance séborrhéique (brillance) - A2 : présence de lésions rétentionnelles (comédons fermés et ouverts) - A3 : présence de lésions inflammatoires (papules et pustules) -A4 : Infiltration des lésions - A5 : présence de macrocystes ou abcès A6 : évaluation de la dilatation des pores - A7 : évaluation de l'homogénéité du grain de la peau (lissage) - A8 : score de l'acné. Les résultats sont présentés ci-dessous : Variation / placebo (%) Al -3 A2 -2 A3 -20 A4 -22 A 5 -40 A6 -5 A7 + 21 A8 -7 On constate qu'après 28 jours d'applications biquotidiennes et en comparaison au placebo, le principe actif selon l'invention améliore les différents items étudiés par évaluation clinique. b - comptage des lésions Les résultats relatifs à l'étude des photographies, présentés dans le tableau qui suit, montrent qu'après 28 jours d'applications biquotidiennes, le principe actif selon l'invention entraîne une diminution de 20% du nombre de lésions permanentes au niveau du visage. Placebo Principe actif 4% JO J28 JO J28 Moyenne 10 11 12 10 Variation / placebo (%) -20 Après 28 jours d'applications biquotidiennes, le principe actif selon l'invention permet donc d'améliorer toutes les manifestations caractéristiques des peaux à tendance acnéique. 4/ COMPOSITION COSMETIQUE INCLUANT LE PRINCIPE ACTIF SELON L'INVENTION : La présente invention couvre aussi les compositions cosmétiques incluant le principe actif selon la présente invention dans différentes formes galéniques, notamment gel, solution, émulsion, crème.... Il convient alors d'analyser la stabilité des formes galéniques incluant le principe actif selon l'invention, ceci dans des proportions comprises entre 1 et 5 %. La stabilité est caractérisée par une absence de précipitation de l'actif, une absence de crémage et une absence de déphasage. On peut citer des formulations ayant montré une stabilité physique incluant 5% de principe actif selon l'invention. - Carbopol : 0,5% avec Triéthanolamine qsp pl-I=6,5 - Phénonip : 0,7% - Principe actif 5,0% - Eau:93,8% - Sépigel 305: 2,0% - Phénonip : 0,7% - Principe actif : 5,0% - Eau:92,3% - Montanov 202: 3,0% - Isopropyl palmitate : 12,0% Phénonip : 0,7% - Viscolam AT 64 : 2,0% - Principe actif : 5,0% Gel limpide : Gel opaque : Gel émulsionné : 5 10 15 20 - Eau : 77,3% Emulsion non ionique : - Montanov 202 : 3,0% -Simulsol 165: 2,0% - Isopropyl palmitate : 20,0% - Phénonip : 0,7% -Principe actif : 5,0% - Eau : 69,3% Emulsion anionique : - Acide stéarique : 7,0% - Triethanolamine : 3,5% Isopropyl palmitate : 20,0% - Phénonip : 0,7% - Principe actif 5,0% Eau:63,8% Emulsion cationique : -Quaternium-82 : 5,0% - Alcool cétylique : 2,0% - Isopropyl palmitate : 15,0% - Alcool cétéarylique : 1% - PEG 100 stéarate : 1% - Phénonip : 0,7% - Principe actif 5,0% - Eau : 71,3% De plus, des tests ont montré la compatibilité du principe actif avec les matières premières utilisées en cosmétique. Between OJ and J27, the active ingredient according to the invention and the placebo are applied twice a day. At D28, a dermatological evaluation is performed again and high-resolution photographs are taken of each of the volunteers' hemispheres. a - Dermatological evaluation The evaluation is based on a clinical examination performed on the two hemiivisages. The points studied are: - Al: skin with seborrheic tendency (shine) - A2: presence of retention lesions (closed and open comedones) - A3: presence of inflammatory lesions (papules and pustules) - A4: Infiltration of lesions - A5: presence of macrocysts or abscesses A6: evaluation of pore dilation - A7: evaluation of skin grain homogeneity (smoothing) - A8: acne score. The results are shown below: Variation / placebo (%) Al -3 A2 -2 A3 -20 A4 -22 A 5 -40 A6 -5 A7 + 21 A8 -7 After 28 days of twice-daily application and in comparison with placebo, the active ingredient according to the invention improves the different items studied by clinical evaluation. b - counting of the lesions The results relating to the study of the photographs, presented in the following table, show that after 28 days of twice-daily application, the active principle according to the invention causes a 20% decrease in the number of lesions. permanent in the face. Placebo active ingredient 4% OJ J28 OJ J28 Medium 10 11 12 10 Variation / placebo (%) -20 After 28 days of twice-daily applications, the active ingredient according to the invention thus makes it possible to improve all the characteristic manifestations of skins with a tendency to acne. 4 / COSMETIC COMPOSITION INCLUDING THE ACTIVE INGREDIENT ACCORDING TO THE INVENTION: The present invention also covers the cosmetic compositions including the active ingredient according to the present invention in different galenical forms, in particular gel, solution, emulsion, cream .... It is then necessary to analyze the stability of the dosage forms including the active ingredient according to the invention, this in proportions of between 1 and 5%. The stability is characterized by a lack of precipitation of the asset, an absence of creaming and a lack of phase shift. Formulations which have shown a physical stability including 5% of active principle according to the invention. - Carbopol: 0.5% with triethanolamine qspl-I = 6.5 - Phenonip: 0.7% - Active ingredient 5.0% - Water: 93.8% - Sepigel 305: 2.0% - Phenonip: 0 , 7% - Active ingredient: 5.0% - Water: 92.3% - Montanov 202: 3.0% - Isopropyl palmitate: 12.0% Phenonip: 0.7% - Viscolam AT 64: 2.0% - Active ingredient: 5.0% Clear gel: Opaque gel: Emulsified gel: 5 10 15 20 - Water: 77.3% Non-ionic emulsion: - Montanov 202: 3.0% -Simulsol 165: 2.0% - Isopropyl palmitate : 20.0% - Phenonip: 0.7% - Active principle: 5.0% - Water: 69.3% Anionic emulsion: - Stearic acid: 7.0% - Triethanolamine: 3.5% Isopropyl palmitate: 20, 0% - Phenonip: 0.7% - Active ingredient 5.0% Water: 63.8% Cationic emulsion: -Quaternium-82: 5.0% - Cetyl alcohol: 2.0% - Isopropyl palmitate: 15.0% - Cetearyl alcohol: 1% - PEG 100 stearate: 1% - Phenonip: 0.7% - Active ingredient 5.0% - Water: 71.3% In addition, tests have shown the compatibility of the active ingredient with raw materials used in cosmetics than.
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| FR2931675A1 (en) * | 2008-05-29 | 2009-12-04 | Occitane L | Cosmetic or dermatological composition, useful e.g. for cosmetic treatment e.g. to tighten pores, and inhibit growth of Staphylococcus aureus, comprises rice extract, rice vinegar, matte powder, meadowsweet extract and essential oil |
| FR2965483A1 (en) * | 2010-10-04 | 2012-04-06 | Silab Sa | COSMETIC USE OF A TROPAEOLUM MAJUS EXTRACT AS AN ACTIVE INGREDIENT TO PROMOTE OXYGENATION OF SKIN TISSUE |
| US10300012B2 (en) | 2013-12-31 | 2019-05-28 | Virbac | Topical composition comprising extracts of boldo and of meadowsweet, intended for an animal, and uses thereof |
| WO2023148428A1 (en) | 2022-02-02 | 2023-08-10 | Lumene Oy | Use of nordic plant-based ingredients for supporting a healthy skin microbiome |
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| FR2931675A1 (en) * | 2008-05-29 | 2009-12-04 | Occitane L | Cosmetic or dermatological composition, useful e.g. for cosmetic treatment e.g. to tighten pores, and inhibit growth of Staphylococcus aureus, comprises rice extract, rice vinegar, matte powder, meadowsweet extract and essential oil |
| FR2965483A1 (en) * | 2010-10-04 | 2012-04-06 | Silab Sa | COSMETIC USE OF A TROPAEOLUM MAJUS EXTRACT AS AN ACTIVE INGREDIENT TO PROMOTE OXYGENATION OF SKIN TISSUE |
| WO2012045974A3 (en) * | 2010-10-04 | 2012-10-18 | Societe Industrielle Limousine D'application Biologique | Cosmetic use of a tropaeolum majus extract as an active principle for promoting the oxygenation of skin tissue |
| US10300012B2 (en) | 2013-12-31 | 2019-05-28 | Virbac | Topical composition comprising extracts of boldo and of meadowsweet, intended for an animal, and uses thereof |
| WO2023148428A1 (en) | 2022-02-02 | 2023-08-10 | Lumene Oy | Use of nordic plant-based ingredients for supporting a healthy skin microbiome |
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