EP4135735A1 - Active principle comprising a peel extract of immature punica granatum fruit and uses for preventing and/or combatting acne - Google Patents
Active principle comprising a peel extract of immature punica granatum fruit and uses for preventing and/or combatting acneInfo
- Publication number
- EP4135735A1 EP4135735A1 EP21716954.9A EP21716954A EP4135735A1 EP 4135735 A1 EP4135735 A1 EP 4135735A1 EP 21716954 A EP21716954 A EP 21716954A EP 4135735 A1 EP4135735 A1 EP 4135735A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- active principle
- acne
- principle according
- hydrolyzate
- skin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
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- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 230000036620 skin dryness Effects 0.000 description 1
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- 239000000600 sorbitol Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229920001864 tannin Polymers 0.000 description 1
- 239000001648 tannin Substances 0.000 description 1
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- 150000003515 testosterones Chemical class 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
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- 239000011787 zinc oxide Substances 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/10—Anti-acne agents
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- 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)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/08—Antiseborrheics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/008—Preparations for oily skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/10—Preparation or pretreatment of starting material
- A61K2236/19—Preparation or pretreatment of starting material involving fermentation using yeast, bacteria or both; enzymatic treatment
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation or decoction
Definitions
- the invention relates to an active principle for the specific skin comprising a hydrolyzate of the peel of immature fruits of Punica granatum, useful in cosmetics or dermatology in particular for preventing and / or combating acne.
- the invention also relates to cosmetic or dermatological compositions including it, a process for obtaining such an active principle as well as its uses.
- Acne involves four major biological components which are the modification of the activity of the sebaceous gland, hyperkeratinization, modification of the skin microbiota by colonization of the bacteria Cutibacterium acnes (C. acnes) and inflammation. . These four pathophysiological components of acne are biologically linked because they all have an impact on each other without forming a vicious circle.
- the objective of the invention is to respond to this problem by proposing an active principle capable of effectively combating the multiplicity of parameters at the origin of acne.
- the invention relates to a cosmetic or dermatological active principle comprising at least one particular extract of Punica granatum.
- Punica granatum or pomegranate is very well known and widely used.
- the pomegranate fruit can be eaten fresh, in syrup, in juice, the dried arils (whole, powder or molasses).
- the pomegranate fruit peel has astringent, anti-bacterial, anti-haemorrhagic, anti-inflammatory properties
- a pomegranate bark decoction or powder is used for the treatment of gastrointestinal diseases
- extracts are used in particular as antioxidants, in capillaries and as skin cleansers.
- extracts of pomegranate bark for anti-acne applications, in particular ethanolic extracts alone or in combination with other extracts, to reduce the amount of secreted sebum, minimize pores and for an anti-bacterial effect.
- the inventor has demonstrated that these existing extracts of pomegranate bark do not exhibit satisfactory results for preventing or combating all the biological components of acne.
- the inventor has selected a precise step in the ripening of the fruits of Punica granatum and a particular type of extraction.
- the subject of the invention is therefore a particular cosmetic or dermatological active principle, namely an active principle comprising at least one hydrolyzate of the peel of immature fruits of Punica granatum, as well as its use in application to the skin to prevent and / or fight acne.
- a subject of the invention is also a process for obtaining such an active principle as well as the compositions including it suitable for topical application to the skin.
- the particular selection of immature fruits of Punica granatum combined with an enzymatic hydrolysis makes it possible to fight effectively against acne, in particular to fight effectively against the four major components of acne: changes in sebogenesis, l 'hyperkeratinization, inflammation, and changes in microbiota.
- Figure 1 shows the chromatographic profile between 250 and 390 nm of an extract of the bark of immature fruits of Punica granatum.
- Figure 2 shows the chromatographic profile between 250 and 390 nm of an extract of the bark of mature fruits of Punica granatum.
- Figure 3 shows the chromatographic profile between 250 and 390 nm of the juice of Punica granatum.
- cosmetic or dermatological active or “cosmetic or dermatological active principle” within the meaning of the invention, is meant at least one molecule, preferably a set of molecules having an effect on the skin.
- extract of a raw material X, within the meaning of the present invention, is meant any molecule or mixture of at least two molecules obtained from a raw material X, regardless of the process for extracting said molecule (s). It may for example be an extract obtained by aqueous and / or hydroalcoholic and / or hydroglycolic extraction, etc.
- hydrolyzate of a raw material X within the meaning of the invention is meant any extraction obtained from a raw material X, by a process comprising at least one enzymatic or chemical hydrolysis step of an aqueous extract.
- the hydrolyzate is in liquid form.
- enzymatic hydrolyzate of a raw material X within the meaning of the invention, is meant any extraction obtained from a raw material X by a process comprising at least one step of enzymatic hydrolysis of an extract aqueous.
- hydroglycolic extract of a raw material X within the meaning of the invention, is meant any extract obtained from a raw material X by a process comprising as main step an extraction step using at least a mixture of at least two solvents (water and a glycolic solvent, such as for example butylene glycol).
- aqueous extraction of a raw material X within the meaning of the invention is meant any extract obtained from a raw material X by a process comprising water as the sole extraction solvent.
- film within the meaning of the invention is meant a cosmetic product which is applied momentarily to the skin and which is removed after a certain application time, exhibiting a cosmetic or dermocosmetic effect. It may for example be a face mask.
- dry film within the meaning of the invention is meant a film having a water activity of less than 0.6.
- water activity is meant within the meaning of the invention a parameter well known to those skilled in the art making it possible to know the availability of water in the material. It can be measured using a device called AWmeter such as a LabSift-aw type AWmeter. The value is unitless, it is between 0 and 1. This parameter is different from the water content.
- water content of the dry film is understood to mean the amount of liquid water contained in the film (ratio of the weight of water to the total weight of the film) and is measured by successive weighings before and after drying in the film. oven.
- Ellagitannins polyphenolic compounds also called ellagic tannins.
- the invention therefore relates to a specific active principle, particularly useful for preventing and / or combating acne.
- Said active principle is a cosmetic or dermatological active principle comprising at least one particular hydrolyzate of Punica granatum.
- the active principle is obtained from the peel of immature fruits of Punica granatum.
- the choice of this stage of fruit maturity is essential because it contains different molecules or the same molecules but in different quantities, from those contained in the rind of mature fruits of Punica granatum.
- Punica granatum fruits: - which have a diameter less than 10 cm, preferably less than 8cm, and / or
- the active principle according to the invention is a hydrolyzate, that is to say that it is obtained by a process comprising a step of hydrolysis of an aqueous extract.
- it is an enzymatic hydrolyzate, even more preferably an enzymatic hydrolyzate obtained by hydrolysis carried out using at least one carbohydrase.
- it is an aqueous hydrolyzate, that is to say that before hydrolysis, the bark of Punica granatum has undergone solubilization in water.
- the invention excludes any other extract such as ethanolic or hydroglycolic extracts of Punica granatum.
- the active principle according to the invention can be in liquid form or in powder form or in film form.
- the active principle according to the invention When it is in liquid form, the active principle according to the invention preferably consists exclusively of the hydrolyzate of the peel of immature fruits of Punica granatum and of water, as well as the extraction solvent. Preservatives or stabilizers can be added to facilitate the preservation and industrial use of the active principle.
- the active principle according to the invention in liquid form is preferably in the form of a clear liquid, with a weak odor and an ocher to amber color. It can, however, be more colored and / or be discolored in any method known to those skilled in the art.
- the active principle according to the invention in liquid form has a dry matter content of 10 g / L to 40 g / L.
- the active principle according to the invention consists of:
- the hydrolyzate represents at least 10% by weight of the active principle and the support at most 90%.
- the active principle according to the invention can also be presented in the form of a dry film.
- the hydrolyzate of the peel of immature fruits of Punica granatum preferably represents at least 0.1% by weight of the dry film.
- the active principle comprises:
- the polymer of natural origin can be chosen from: Pectin, Tamarind gum, Alginate, Pullulan, Psyllium, Xanthan, Guar, Tara, Carob, Agar, Gum arabic, Gellan, Dextran, Carrageenan, Cellulose, Konjac and Chitosan.
- the plasticizer can be chosen from: Glycerol, Sorbitol, Sucrose, Erythritol, Urea, Propylene glycol and Butylene glycol.
- the mineral filler can be chosen from: Calcium carbonate, green clay, kaolin, perlite, talc, magnesium silicate, mica, diatomaceous sericite, silica, calcium sulphate, calcium chloride, potassium chloride, iron oxide and zinc oxide.
- the active principle can also comprise a pigment for coloring the film.
- the hydrolyzate comprises polyphenols, sugars, minerals and proteins, and this, whether the active principle is in liquid, solid or film form.
- the hydrolyzate of the active principle according to the invention comprises:
- the active principle when the active principle is in liquid form and that it consists only of the hydrolyzate, the active principle according to the invention comprises these constituents in these proportions.
- the active principle according to the invention comprises:
- phenolic compounds by weight relative to the weight of dry matter of the active principle.
- the content of phenolic compounds can be determined by colorimetric assay.
- the phenolic compounds form, in the presence of potassium ferricyanide and iron chloride, colored complexes which can be determined by spectrophotometry at 715 nm. The intensity of this coloration is proportional to the quantity of phenolic compounds present in the sample.
- Calibration solutions are prepared from a gallic acid or ellagic acid standard of 40 to 120 mg / L, preferably ellagic acid. A calibration curve of the optical densities of the calibration solutions as a function of their concentration is constructed. The samples are diluted beforehand with distilled water so that the polyphenol content corresponds to the calibration range. The amount of polyphenols in the samples is determined using the calibration curve.
- the phenolic compounds of the active principle according to the invention can be characterized by any suitable method, in particular by liquid chromatography coupled to mass spectrometry.
- the polyphenols present in the hydrolyzate are Ellagitannins.
- the Ellagitannins present in the hydrolyzate are preferably at least 50% Punicalagin and its derivatives, less than 40% Punicalin, less than 20% HHDP derivatives and less than 10% Ellagic acid.
- the active principle according to the invention comprises the Ellagitannins presented in Table 1.
- the total sugar content can be determined using the DUBOIS method (Dubois M. et al. Analytical chemistry, 28, 3, 350-356, 1956). All the reducing functions are released in the presence of concentrated sulfuric acid and together with the phenol give a yellow-orange colored compound. The coloration obtained, measured at 490 nm on a spectrophotometer, is proportional to the quantity of total sugars in the sample.
- the determination of the molar masses of the sugars is carried out by HPLC with RI detection.
- the carbohydrate fraction of the active principle according to the invention in powder form is preferably composed of 55% to 65% of oligosaccharides and of 35% to 45% of polysaccharides consisting of glucose and fructose.
- the average size of sugars is an average molar mass of 13,140 Da.
- the carbohydrate fraction of the active principle in liquid form is preferably composed of 85 to 100% of oligosaccharides consisting of glucose and fructose. Their sizes are less than 3600Da.
- the determination of the proteins in the active principle according to the invention can be carried out in particular by the method of KJELDHAL (reference: Official method of analysis of the AOC, 12th ed. W Horwitz, ED, New York, 15-60, 1975).
- the protein content is expressed as a percentage relative to the dry matter content.
- the crude ash content can be determined by weighing the residues resulting from the incineration of the samples of the extract according to the invention at 550 ° C. in an electric muffle furnace.
- the minerals present in the active principle are mainly potassium, sodium and chlorine. Other minerals such as phosphorus, magnesium, and sulfur may be present.
- the analysis of the minerals constituting the ashes of the active principle according to the invention can be carried out by optical emission spectrometry (ICP / OES) and the determination of the chloride ions by titration with silver nitrate.
- the hydrolyzate of the peel of immature fruits of Punica granatum according to the invention can be obtained by any means. Preferably, it is obtained by carrying out a process comprising at least one aqueous extraction and one enzymatic hydrolysis.
- the hydrolyzate according to the invention is obtained by carrying out the following steps: a) Solubilization of powder from the peel of immature Punica granatum fruits in water, at a rate of at least 50 g / L, b) Enzymatic hydrolysis, preferably using a carbohydrase, c) Separation of the soluble and insoluble phases, by any means making it possible to separate an insoluble phase from the soluble phase, for example by centrifugation , filtration or decantation d) recovery of the soluble phase, and enzymatic inactivation by any means allowing the inactivation of the enzymatic activities, for example by heat treatment, e) purification of the polyphenolic compounds by any means allowing molecular sorting, f) optionally deodorization or decoloration by adding a process adjuvant allowing deodorization or decoloration g) preferably filtration and sterilizing filtration.
- the hydrolyzate obtained can be used as it is in liquid form and constitutes the active principle according to the invention.
- the hydrolyzate can also optionally be combined with a support and dried (atomization or lyophilization in particular), so as to be in powder form.
- the hydrolyzate can also optionally be combined with compounds allowing its presentation in the form of a dry film.
- compositions comprising a cosmetically / dermatologically acceptable medium. These are compositions in different dosage forms, suitable for topical application to the skin.
- compositions can be in particular in the form of oil-in-water emulsions, water-in-oil emulsions, multiple emulsions (Water / Oil / Water or Oil / Water / Oil) which can optionally be microemulsions or nanoemulsions, or in the form of solutions, suspensions, water dispersions, aqueous gels or powders. They can be more or less fluid and have the appearance of creams, emulsions, gels or films or all other aspects of skin care cosmetics.
- compositions comprising at least 0.1% of an active principle according to the invention in liquid form, preferably between 0.1 and 10% or at least 0.05% of the active principle according to the invention. the invention in powder form, preferably between 0.05% and 2%.
- compositions comprise, in addition to the active agent, a physiologically acceptable medium and preferably cosmetically and / or dermatologically acceptable, that is to say which does not cause unacceptable feelings of discomfort for the user such as redness, tightness or tingling.
- compositions according to the invention may contain as adjuvant at least one compound chosen from:
- oils which can be chosen in particular from silicone oils, linear or cyclic, volatile or non-volatile;
- waxes such as ozokerite, polyethylene wax, beeswax or wax carnauba,
- surfactants preferably emulsifiers, whether nonionic, anionic, cationic or amphoteric,
- humectants such as polyols such as glycerin
- compositions are in particular intended to be used for improving the quality of the skin, in particular for preventing and / or combating acne.
- the composition comprising the cosmetic active principle according to the invention is applied, preferably to the face, at least once a day for at least 14 days.
- compositions according to the invention are particularly effective for a topical treatment of the skin and in particular for an effect of preventing or treating acne.
- a subject of the invention is therefore also an active principle according to the invention or a composition including it for its use in the prevention and / or treatment of acne.
- the invention relates to the use of a hydrolyzate of the peel of immature fruits of Punica granatum for preventing and / or combating acne.
- the active principle according to the invention is capable of having a positive influence on these four biological components of acne.
- the active principle according to the invention is capable of acting on the various factors increasing sebogenesis.
- various endogenous (eg hormones, C. acnes, lipophagic activity) and exogenous (eg stress) factors the metabolism of the sebaceous glands is activated, characterized by quantitative and qualitative modifications of the sebum. This results in an increase in sebogenesis and consequently in an abnormally high production of sebum.
- the active principle according to the invention is also capable of acting on hyperkeratinization, another component of acne.
- Hyperkeratinization is an early biological event in the development of acne lesions. It is characterized by an abnormality of proliferation and keratinization of follicular keratinocytes favoring obstruction of the excretory duct, poor evacuation of sebum and consequently dilation of the pilosebaceous duct at the origin of the formation of a microcomedon.
- the active principle according to the invention also acts on inflammation, the third component of acne.
- Inflammation is the biological phenomenon concomitant with all the stages of the formation of acne lesions: microcomedon, comedo, inflammatory lesion, post-inflammatory erythema and even scar.
- the bacterium C. acnes plays an essential role in the appearance of inflammatory lesions. It stimulates the production of pro-inflammatory mediators by several cell types of the pilosebaceous unit (keratinocytes, sebocytes, immune cells infiltrating acne lesions).
- the active principle according to the invention has the capacity to act on the cutaneous microbiota of acne-prone skin.
- C. acnes The Cutibacterium acnes bacteria (C. acnes) is considered to be one of the major pathogenic factors contributing to the development of acne. Acne is characterized by a loss of phylotypic diversity of C. acnes in favor of the IA1 phylotype.
- the population of C. acnes phylotype IA1 has an ability to communicate and organize itself to set up virulence factors (eg formation of biofilms) via the quorum sensing system and thus colonize the follicle.
- the active principle according to the invention restores the homeostasis of acne-prone skin.
- the sebaceous glands are sensitive to androgens. They have the enzymatic equipment necessary for the metabolism of testosterone into dihydrotestosterone (DHT) and specific receptors for DHT. Stimulation of these receptors activates genes involved in the production of sebum.
- DHT dihydrotestosterone
- Stimulation of these receptors activates genes involved in the production of sebum.
- DHT dihydrotestosterone
- the number of receptors for DHT is increased in the acne sufferer as well as his sensitivity to DHT. This is why acne is considered "a peripheral hormonal disease".
- the active principle according to the invention inhibits the conversion of testosterone into DHT, and thus limits the excess of androgens involved in the pathophysiology of acne.
- Sebum is a substrate of choice for the growth of microorganisms contributing to the development of acne, such as C. acnes, it has been shown that C. acnes has an activity which stimulates lipogenesis. In acne, the hyperproliferative bacteria would be able to stimulate directly, or indirectly via soluble factors, the production of lipid droplets by the sebocytes. By this mechanism, C. acnes is able to aggravate hyperseborrhea, a major pathophysiological component of acne.
- the active principle according to the invention limits the secretion of lipids in the sebocytes.
- the active principle according to the invention inhibits the secretion of lipids induced by substance P or by the combination of C. acnes and substance P on sebocytes.
- the active principle according to the invention makes it possible to normalize the activity of the sebaceous gland, a key biological component of pathophysiology acne.
- the active principle according to the invention is also capable of acting on the hyperkeratinization which occurs in acne.
- Hyperkeratinization is an early biological event in the development of acne lesions. This is an abnormality in the proliferation and keratinization of the keratinocytes that line the wall of the follicle. It leads to an accumulation of corneocytes and obstruction of the excretory duct. These changes alter the normal evacuation of sebum causing retention and dilation of the pilosebaceous duct, causing the formation of a microcomedon. The latter is a preclinical lesion invisible to the naked eye characterized histologically by the distension of the wall of the follicle and which progressively progresses to the comedo.
- cytokeratin-16 CK-16
- Squalene a component of sebum, is the main source of peroxidized lipids in acne-prone skin. Beyond causing skin irritation, peroxidized squalenes exert a strong comedogenic power, colonization by C. acnes.
- C. acnes By colonizing the pilosebaceous duct, C. acnes is able to modify the biology of keratinocytes and influence their proliferation and differentiation.
- the bacterium stimulates the synthesis of pro-inflammatory cytokines in the pilosebaceous follicle, in particular interleukin la (IL-la), a major factor in the appearance of hyperkeratinization.
- IL-la interleukin la
- this cytokine is capable of activating the genes encoding cytokeratins, in particular CK-16, but also of inducing the production of other keratins such as CK-5.
- studies have shown that C. acnes is able to exert a direct effect on the biology of keratinocytes and the formation of microcomedones.
- a hydrolyzate of the peel of immature fruits of Punica granatum according to the invention is capable of having an effect on the hyperkeratinization which occurs in acne.
- the active principle according to the invention is capable of:
- the active principle according to the invention is also capable of acting on the inflammation which occurs in acne.
- Inflammation is a fundamental process present throughout the development of acne lesions. Indeed, it is present from the early stages to the later stages of the pathology.
- C. acnes actively participates in the creation of an inflammatory environment.
- the bacteria By colonizing the pilosebaceous follicle, the bacteria play an essential role in triggering the inflammatory reaction and the appearance of inflammatory lesions. It stimulates the production of inflammation mediators by several cell types of the pilosebaceous unit.
- exogenous and endogenous factors such as hormones, stress, composition of sebum, etc., accentuate the inflammatory phenomenon.
- keratinocytes Several cell types of the pilosebaceous follicle are involved in these inflammatory mechanisms: keratinocytes, sebocytes but also immune cells infiltrating acne lesions.
- the modification of the composition of the sebum and in particular the peroxidation of squalenes influences the inflammatory state of the pilosebaceous follicle by stimulating the secretion of the pro-inflammatory cytokine IL-Ia by the keratinocytes.
- colonization of the pilosebaceous follicle by C. acnes leads to the production and secretion by the keratinocytes of numerous pro-inflammatory mediators:
- MMP2 - metalloproteinases
- the active principle according to the invention inhibits the secretion of chemokines, cytokines and metalloproteinases in reconstructed 3D epidermis mimicking acne-prone skin.
- Sebocyte inflammation [0126] Sebocyte inflammation.
- Acne is characterized by a change in the composition of the microenvironment of the sebaceous follicles inducing colonization and increased metabolic activity of C. acnes.
- the bacteria are able to induce an inflammatory response at the level of the sebocytes which produce numerous pro-inflammatory mediators.
- sebocytes secrete pro-inflammatory cytokines (IL-6, IL-8, etc.) contributing to the inflammatory reaction observed in acne lesions.
- the secretion of these mediators confers on the sebocytes the capacity to promote the differentiation of the naive helper T lymphocytes into Th17, thus reinforcing the inflammatory phenomenon.
- the sebaceous gland is sensitive to negative emotions such as stress. It has been shown that acne patients exhibit increased innervation in the environment of the sebaceous glands indicating the existence of communication between the nervous and sebaceous systems.
- substance P as a neurotransmitter of inflammation in acne has so far been well described in the literature. It causes the secretion of pro-inflammatory cytokines (IL-6, IL-8, etc.) exacerbating the inflammatory environment of the sebaceous glands.
- an infiltrate of immune cells is present in the acne lesions, an infiltrate composed mainly of CD4 + helper T lymphocytes.
- Thl7 Thl7 lymphocytes contribute significantly to the inflammatory phenomenon.
- C. acnes has been shown to have the ability to induce differentiation of naive lymphocytes into Th17 lymphocytes.
- IL-17 interleukin 17
- the presence of IL-17 results in the secretion of pro-inflammatory mediators by epithelial cells, such as IL-8 and CCL20, thereby exacerbating the inflammatory process.
- the appearance and exacerbation of the inflammatory phenomenon described in acne lesions therefore involves various protagonists and factors.
- the inflammatory mediators produced promote comedogenesis and then the rupture of the follicle leading to the appearance of inflammatory lesions.
- the active principle is capable of regulating the biology of LThl7 and of limiting the inflammation induced by these cells.
- a hydrolyzate of the peel of immature fruits of Punica granatum is capable of having an effect on the inflammation which occurs in acne.
- the active principle according to the invention is capable of:
- a marker of the pathophysiology of acne in particular by inhibiting the secretion of CCL5, of CCL20, of CXCL1, and by inhibiting the secretion of IL-Ia, of IL-8, and inhibiting the secretion of MMP2 and MMP9;
- the active principle according to the invention is capable of acting against C. acnes.
- Cutibacterium acnes is a major species of the cutaneous commensal flora, the preferred habitat of which is the pilosebaceous follicle. This bacteria is considered to be one of the major pathogenic factors contributing to the development of acne. Studies on C. acnes and its role in acne have brought to light new data and mechanisms explaining its virulence in pathology.
- the bacterial component is therefore an important parameter in the development of acne lesions. Targeting the bacterium C. acnes phylotype IA1 and reducing its virulence is an essential strategy to fight against this pathology.
- the active principle according to the invention limits the growth of the bacterium C. acnes phylotype IA1.
- the microcomedones constitute anaerobic microenvironments rich in lipids, favorable to the growth and establishment of C. acnes. Indeed, the latter can behave like an opportunistic pathogenic bacterium thanks to a mode of growth in biofilm.
- the biofilm is a heterogeneous structure made up of the bacterial population enclosed in an extracellular matrix of DNA, proteins and polysaccharides produced by it, all adhering to a surface. This biofilm growth gives bacteria specific properties of morphology, growth, communication and resistance to biocides in order to optimize their survival.
- QS quorum sensing
- the active principle according to the invention also exhibits an anti-bacterial effect against the bacteria which are involved in acne, in particular C. acnes of phylotype IA1.
- the direct anti-bacterial efficacy of the active principle according to the invention is real since it
- the active principle according to the invention is capable of targeting the four major components of the pathophysiology of acne. It normalizes the activity of the sebaceous gland. It also has keratolytic activity and controls colonization by C. acnes. It reduces the inflammatory sebocytic, keratinocyte and lymphocyte responses of the Thl7 type. Finally, it acts directly as an anti-bacterial by limiting the growth of C. acnes and by inhibiting quorum sensing and the formation of a bacterial biofilm. [0148] Its therapeutic efficacy has been clinically demonstrated on adult volunteers suffering from mild to moderate acne: the number of acne lesions is significantly reduced with a lower GEA score. This active ingredient improves the quality and appearance of acne-prone skin. It is a high-performance treatment combining speed of action and efficiency in the daily care of acne-prone skin.
- the invention relates to the use of an active principle comprising a hydrolyzate of the peel of immature pomegranate fruit on acne-prone skin for:
- the invention thus also relates to a non-therapeutic process, namely a non-therapeutic cosmetic process for treating the skin for an anti-acne effect, which consists in the topical application to the skin of a composition comprising a principle. active according to the invention.
- Example of active principles and comparison with existing pomegranate extracts [0154] IV.A1.
- Example 1 Example of Active Principle According to the Invention in Liquid Form
- the active principle is obtained by carrying out the following steps: a) Solubilization of powder from the peel of immature Punica granatum fruits in water, at a rate of 50g / L, b) Enzymatic hydrolysis using a carbohydrase, c) Separation of the soluble and insoluble phases, by centrifugation, d) recovery of the soluble phase, and enzymatic inactivation by heat treatment, e) purification by filtration of the polyphenolic compounds, f) deodorization by addition of a process adjuvant allowing deodorization, g) filtrations and sterilizing filtration.
- the polyphenols of the hydrolyzate are Ellagitannins, more precisely, they are Punicalagin and its derivatives, Punicalin, HHDP derivatives and Ellagic acid.
- Example 2 Example of Active Principle According to the Invention in Powder Form
- the active principle is obtained by carrying out the following steps: a) Solubilization of powder from the peel of immature Punica granatum fruits in water, at a rate of 50g / L, b) Enzymatic hydrolysis using a carbohydrase, c) Separation of the soluble and insoluble phases, by centrifugation, d) recovery of the soluble phase, and enzymatic inactivation by heat treatment , e) purification by filtration of the polyphenolic compounds, f) introduction of maltodextrin, at a rate of 90% (v / v), g) concentration, sterilization and atomization.
- the active principle comprising the hydrolyzate according to the invention and a support, obtained by implementing the method described above, has the following analytical characteristics:
- the polyphenols present in the hydrolyzate are Ellagitannins. These are Punicalagin and its derivatives, Punicalin, HHDP derivatives and Ellagic acid.
- Example 3 example of active principle according to the invention in the form of a film.
- the active principle in the form of a film containing the active principle can be obtained by the following process: a) Solubilization of powder of the peel of immature Punica granatum fruits in water, at a rate of 50 g / L, b) Enzymatic hydrolysis using a carbohydrase, c) Separation of the soluble and insoluble phases, by centrifugation, d) recovery of the soluble phase, and enzymatic inactivation by heat treatment, e) purification by filtration of the polyphenolic compounds, f) addition of polymers of natural origin, plasticizers, mineral fillers and surfactant g) deposit of the solution on a support h) evaporation of water in an oven heated to a temperature between 70 and 100 ° C i ) laser cutting according to the desired shape.
- the active principle according to the invention obtained by carrying out the process described above has the following composition: 28.3% of polymers of natural origin including carrageenans, guar and cellulose, 49 , 5% plasticizers including urea and glycerol, 20.5% mineral fillers including silica and kaolin and 1.2% surfactant and 0.5% extract of immature Punica granatum.
- an "immature" fruit harvested at the beginning of summer has a green rind, a diameter of less than 8 cm and exhibits particular markers (high content of punicalagin & derivatives), while that a “mature” fruit harvested at the end of autumn, has an orange / red peel, a diameter greater than 10 cm and has different markers (high punicalin content).
- the pomegranate peels available on the market are a by-product of the pomegranate juice industry. Thus, the pomegranate peels from this industry are always mature pomegranate peels, so that the pomegranate juice is sweet and sweet in taste.
- Table 5 shows the results comparing an ethanolic extract and an aqueous extract.
- the ethanolic extract is obtained by dissolving pomegranate peel powder at a rate of 50 g / L in absolute ethanol. It is compared with an aqueous extract obtained in a similar manner by dissolving pomegranate peel powder at a rate of 50 g / L in distilled water.
- the aqueous extract has a much higher content of Ellagitannins compounds than the ethanolic extract.
- Example 4 Example of the Composition of a Purifying Lotion According to the Invention An example of a formulation containing an active principle according to the invention is presented in Table 7 below. This lotion is fresh and non-sticky, it gently purifies the skin.
- Example 5 Example of a Treating Serum Composition According to the Invention
- Table 8 An example of a formulation containing an active principle according to the invention is presented in Table 8 below. This light and slippery treatment spreads easily and penetrates quickly, leaving the skin soft without leaving a greasy or sticky feeling. [0196] [Table 8]
- Acne is a pathology characterized by quantitative and qualitative changes in sebum. Indeed, under the influence of various endogenous (eg hormones, Cutibacterium acnes, lipophagic activity) and exogenous (eg stress) factors, the metabolism of the sebaceous glands is activated. This results in an increase in sebogenesis and consequently in an abnormally high production of sebum.
- endogenous eg hormones, Cutibacterium acnes, lipophagic activity
- exogenous eg stress
- the objective of this study was to evaluate the effect of an active principle according to the invention on the sebaceous component, the activity of which is modified by androgenic hormones.
- the activity of 5-alpha reductase was evaluated in vitro on primary human sebocytes (SHN). This enzyme catalyzes the conversion of testosterone to dihydrotestosterone (DHT).
- SHN normal human sebocytes
- DHT dihydrotestosterone
- the operating protocol for the culture and the treatment of human sebocytes for the study of the metabolism of testosterone is as follows. Normal human sebocytes (SHN) are seeded in a specific culture medium and incubated at 37 ° C. In a first, the cells are then pretreated with the active principle of Example 2 at 0.0006% or 0.0015%. The next day, the cells are treated with a radiolabeled testosterone solution containing or not the active principle of Example 2 at 0.0006% or 0.0015% for 24 hours. The culture supernatants are recovered. [0206] Analysis of the activity of 5-alpha reductase:
- the steroids contained in the culture supernatants were extracted into a mixture of chloroform / methanol.
- the organic phase, containing the steroids, was collected and the different molecular species (testosterone metabolites) were separated by thin layer chromatography (TLC) using a dichloromethane / ethyl acetate / methanol mixture as separation solvent.
- TLC thin layer chromatography
- the revelation of the chromatography plates and the evaluation of the quantity of transformed testosterone were carried out by densitometric analysis of the different spots corresponding to the different metabolites of testosterone.
- the active principle according to the invention significantly inhibits the conversion of testosterone into DHT by 37%.
- the active principle according to the invention therefore regulates the biology of sebocytes and thus limits the excess of androgens involved in the physiology of acne.
- the objective of this study is to evaluate in vitro the effect of the active principle according to the invention on the sebogenesis, thanks to the analysis of the secretion of lipid droplets by the NHS subjected to a stress by the substance. P and / or C. acnes.
- the operating protocol for the culture and treatment of human sebocytes for the study of sebogenesis is described below.
- Normal human sebocytes (SHN) are seeded in a specific culture medium and incubated at 37 ° C. Then, the cells are treated with a suspension of C. acnes in the presence or absence of substance P for 24 hours.
- the active principle of Example 2 is applied at 0.0006% or 0.0015% together with the C. acnes +/- Substance P treatment. Finally, the cells are rinsed with PBS buffer and then fixed.
- the cells are fixed in paraformaldehyde and the BODIPY TM probe, which stains neutral lipids, is used. The nuclei are marked.
- the results on the sebogenesis are presented in Table 10 (Average values of the coloration of the lipids by the BODIPY TM probe of the NHS treated with C. acnes).
- the active principle according to the invention significantly inhibits the secretion of lipid droplets induced by C. acnes by 62%, by the substance P 87% and the combination of C. acnes and substance P 73%. In response to C. acnes and / or to substance P, the active principle according to the invention thus limits the excess secretion of lipids, a parameter characteristic of the pathophysiology of acne. [0223] C. Study of the effectiveness of the active principle according to the invention on lipophagia of the sebaceous gland.
- the cells are fixed in methanol.
- the primary antibody is used.
- the cores are labeled with 4 ', 6-diamidino-2-phenylindole.
- the visualization is carried out on the microscope coupled to an image analysis system.
- the coloring and the synthesis of the various markers studied are proportional to the intensity of the fluorescence (yellow or green color) present in the NHS.
- the active principle according to the invention significantly increases the synthesis of LC3b by 121% and significantly inhibits the secretion of 77% lipid droplets.
- ACNESIUM ® limits the production of lipids, a characteristic component of the pathophysiology of acne.
- hyperkeratinization is an early biological event in the development of acne lesions. It is characterized by an abnormality of proliferation and keratinization of follicular keratinocytes favoring obstruction of the excretory duct, poor evacuation of sebum and consequently dilation of the pilosebaceous duct at the origin of the formation of a microcomedon.
- the objective of this study was to evaluate the effect of an active principle according to the invention on hyperkeratinization. Hyperkeratinization was assessed by measuring the thickness of the stratum corneum and by studying the synthesis of cytokeratins CK-5 and CK-16 in a model mimicking acne-prone skin (named SILABSKIN ® RE mimic acne).
- SILABSKIN ® RE mimic acne
- Normal human keratinocytes are seeded in inserts in a specific culture medium and incubated at 37 ° C.
- the SILABSKIN ® RE are passed through an air / liquid interface then the culture medium is changed every 2 days.
- the SILABSKIN ® RE are treated topically with a suspension of C. acnes, the active principle of example 2 is applied topically at 0.003% and 0.006% together with the application of C. acnes. After 2 hours, the excess bacterial solution is aspirated.
- the next day the SILABSKIN ® RE are again treated topically with a suspension of C.
- Example 2 the active ingredient of Example 2 was applied topically to 0.003% and 0.006% in conjunction with the application of C. acnes. After 2 hours, the excess bacterial solution is aspirated. SILABSKIN ® RE are finally treated topically with a solution of peroxidized squalene. Finally, the sub-swim-culture are recovered and stored at -80 ° C and tissues were collected and fixed in paraformaldehyde .After fixation, SILABSKIN ® RE are dehydrated and embedded in paraffin. Sections are made using a microtome.
- the hematoxylin / eosin staining is carried out.
- the immunohistological analyzes of cytokeratins-5 and -16 were carried out after incubation of the primary antibodies, followed by incubation with the secondary antibody.
- the cores are labeled with 4 ', 6-diamidino-2-phenylindole.
- the visualization is carried out on the microscope coupled to an image analysis system.
- the synthesis of the various markers studied is proportional to the intensity of the fluorescence (green color) present on the reconstructed epidermis.
- a quantitative analysis of the images was carried out using Matlab software.
- the cells are then incubated at 37 ° C. in an atmosphere containing 5% CO 2.
- the cells are recovered and the total RNAs extracted for the study of filaggrin, loricrin, claudin-4, GBA and ABCA12.
- the RNAs were reverse-transcribed and the complementary DNAs obtained were analyzed by the quantitative PCR technique.
- the mRNAs of reference controls were also analyzed in parallel with the mRNAs of filaggrin, claudin-4, GBA and ABCA12.
- the quantification of the incorporation of fluorescence (SYBR Green) is measured continuously using a thermal cycler.
- Ct analysis is performed using software. The results are presented in Tables 33 and 34 below.
- the active principle according to the invention induces the expression of mRNAs encoding filaggrin and does not induce the expression of mRNAs encoding Loricrin, Claudine-4, ABCA12 and GBA.
- inflammation is the biological phenomenon concomitant with all the stages of the formation of acne lesions: microcomedon, comedone, inflammatory lesion, post-inflammatory erythema and even scar.
- the C. acnes bacterium stimulates the production of pro-inflammatory mediators by several cell types of the pilosebaceous unit (keratinocytes, sebocytes, immune cells infiltrating acne lesions).
- the objective of these studies was to evaluate the effect of an active principle according to the invention on keratinocyte inflammation, sebocytic inflammation and on the biology of Th17 lymphocytes.
- the keratinocyte inflammation was studied on a 3D model mimicking acne skin (called SILABSKIN ® RE mimic acne) assaying various mediators of inflammation, found in large quantities in acne-prone skin: CCL5, CCL20, CXCL1, IL-1a, IL-8, MMP2 and MMP9.
- SILABSKIN ® RE mimic acne
- Normal human keratinocytes are seeded in inserts in a specific culture medium and incubated at 37 ° C.
- the SILABSKIN ® RE are passed through an air / liquid interface then the culture medium is changed every 2 days.
- the SILABSKIN ® RE are treated topically with a suspension of C. acnes, the active principle according to the invention is applied topically at 0.003% and 0.006% together with the application of C. acnes.
- SILABSKIN ® RE After 2 hours, the excess bacterial solution is aspirated. The next day the SILABSKIN ® RE are again treated topically with a suspension of C. acnes, the active principle according to the invention is applied topically to 0.003% and 0.006% in conjunction with the application of C. acnes. After 2 hours, the excess bacterial solution is aspirated. SILABSKIN ® RE are finally treated topically with a solution of peroxidized squalene. The culture sub-swimmers of the SILABSKIN ® RE are recovered and stored at -80 ° C.
- Th17 inflammatory response The effect of the active principle according to the invention was evaluated on the Th17 inflammatory response. This study relates to the analysis of the secretion of IL-17 produced by Thl7 lymphocytes, cells found in large numbers in lesion areas of acne.
- Naive T (LT) lymphocytes are isolated from peripheral blood mononuclear cells. They are seeded in plates pre-coated with an anti-CD3 antibody containing specific medium. A mix allowing the differentiation of naive LT into LThl7 is added. The cells are then incubated at 37 ° C. After several days, the culture medium is removed and replaced by a medium containing the differentiation mix in the presence or absence of the active principle according to the invention (0.0015% or 0.0060%). The next day, the cell culture supernatants are collected and stored at -80 ° C. [0283] The secretion of IL-17 was evaluated by the ELISA technique.
- the active principle according to the invention significantly inhibits the secretion of IL-17 by 38%.
- the active principle according to the invention regulates the biology of LThl7 and thus limits the inflammation induced by these cells, which are important actors in the pathophysiology of acne.
- C Study of the effectiveness of the active principle according to the invention on sebocytic inflammation.
- C. acnes induces an inflammatory response in the sebocytes.
- the latter then produce numerous mediators (IL-6, IL-8, etc.) which contribute to the inflammatory reaction observed in acne lesions.
- mediators IL-6, IL-8, etc.
- substance P as a neurotransmitter of inflammation in acne has so far been well described in the literature.
- the sebocytic inflammation was studied by analyzing the secretion of IL-6 and IL-8 by sebocytes subjected to bacterial exposure (C. acnes phylotype I Al) and to a neuronal influence (substance P). .
- the operating protocol for the culture and the treatment of human sebocytes is described below.
- Normal human sebocytes (SHN) are seeded in a specific culture medium and incubated at 37 ° C. in an atmosphere containing 5% CO2.
- the cells are treated with a suspension of C. acnes and / or substance P, and the active principle according to the invention is applied at 0.0006% or 0.0015% together with the C. acnes +/- Substance P. treatment.
- the culture supernatants are then collected and stored at -80 ° C.
- the active principle according to the invention significantly inhibits the secretion of IL-6 and IL-8 by 186% and 196% respectively.
- the C. acnes bacterium is considered to be one of the major pathogenic factors contributing to the development of acne.
- Acne is characterized by a loss of phylotypic diversity of C. acnes in favor of the IA1 phylotype.
- the population of C. acnes phylotype IA1 has an ability to communicate and organize itself to set up virulence factors (biofilm formation) via the quorum sensing system and thus colonize the follicle.
- MIC minimum inhibitory concentration
- the population of C. acnes phylotype IA1 possesses an ability to communicate and organize itself in order to set up virulence factors via the quorum sensing system.
- the effect of the active principle according to the invention on quorum sensing was apprehended by measuring the expression of the Lux gene, a pivot gene whose level of activity is linked to that of QS.
- a culture of C. acnes is inoculated with specific broth, in the presence and absence of the active principle according to the invention (0.006%), from a preculture in the exponential growth phase. This culture is carried out at 37 ° C. under anaerobic conditions for 24 hours, and is followed by measuring the optical density at 600 nm. At the end of the 24 hours of growth, the cultures are centrifuged:
- RNAprotect Bacteria Reagent RNA Protect according to the supplier's recommendations. They are then stored dry at -80 ° C. with a view to extracting the total RNAs.
- the culture supernatants are for their part taken, filtered (0.2 ⁇ m) and stored at -20 ° C. with a view to measuring the quantity of AI-2 secreted during growth.
- the bacterium is inoculated from a preculture in exponential phase in the presence or absence of a sub-inhibitory quantity. of the active principle according to the invention (0.006%), in microplates.
- the microplates are incubated anaerobically at 37 ° C for 48 hours to promote the formation of the biofilm.
- the active principle according to the invention prevents significantly the formation of a biofilm by C. acnes phylotype IA1 of 43%.
- the active principle according to the invention exerts an anti-bacterial activity against the virulent phylotype associated with the development of acne lesions.
- the active principle according to the invention is capable of targeting the four major components of the pathophysiology of acne. Trials have also been performed to clinically demonstrate therapeutic efficacy in adult volunteers with mild to moderate acne, including its impact on the lipidoma of acne-prone skin.
- a hydrolyzate of the peel of immature fruits of Punica granatum is capable of having an effect on the quantitative and qualitative modifications of the lipid profile of the. sebum that are involved in acne.
- the active principle according to the invention is capable of:
- the active principle according to the invention is capable of regulating the biology of sebocytes. [0335] A. Study of the effectiveness of the active principle according to the invention on the lipidoma of acne-prone skin.
- the objective of this study was to evaluate the effect of the active principle according to the invention formulated at 0.5% on the lipid profile of the sebum of skin exhibiting mild to moderate acne.
- Placebo group group of 18 women who applied a placebo formula twice a day for 30 days to the entire face.
- Active principle group according to the invention group of 18 women having applied twice daily for 30 days, a formula containing the active principle according to the invention to the entire face.
- the quantity and the nature of the lipids of the sebum were evaluated by sampling, on D0 and D30, followed by the UPLC-MS / MS assays.
- the identification of the species of interest was validated by the injection of standard compounds and the quantification of the species was carried out by addition of deuterated standard compounds at known concentrations.
- active agent according to the invention formulated at 0.5% significantly improves the quality of the lipid profile of sebum in acne sufferers by: significantly reducing the quantity of fatty acid (palmitic acid: -42%, sapienic acid: -61%, oleic acid : -49%, sebaleic acid: -65%); significantly lowering the unsaturated fatty acid / saturated fatty acid ratio by 14%; significantly reducing the amount of squalenes by 28%; significantly reducing the amount of cholesterol by 26%;
- Placebo group group of 46 women who applied the placebo formula to the entire face for 30 days, morning and evening.
- Active principle group group of 46 women having applied for 30 days, morning and evening, the formula containing the active principle according to the invention to the entire face.
- the GEA scale has 6 stages.
- the dermatologist established a clinical condition of the skin by evaluating various parameters relating to the problem of acne-prone skin according to the following 6 criteria on a rating scale ranging from 0 to 9 (from zero to significant): intensity of seborrhea, intensity of erythema linked to pimples, importance of dilated pores, intensity of skin dryness, irregularity of the complexion, irregularity of the relief [0354]
- intensity of seborrhea intensity of erythema linked to pimples
- importance of dilated pores intensity of skin dryness
- irregularity of the complexion irregularity of the relief
- the product reduces dilated pores 5)
- the product has a moisturizing effect
- the product can be used to treat mild to moderate acne
- the group using the formula containing the active principle according to the invention reveals significantly more favorable performance than the placebo group: reduction in the number of lesions 40.6% retention for the group which used the formula containing the active ingredient according to the invention versus 30.9% for the group which applied the placebo formula.
- the results corresponding to the count of the total number of inflammatory lesions are presented in table 43.
- the group using the formula containing the active principle according to the invention shows significantly more favorable performance than the placebo group: reduction in the total number of lesions by 43.9% for the group having used the formula containing the active principle according to invention versus 34.0% for the group which applied the placebo formula.
- the group using the formula containing the active principle according to the invention reveals more favorable performance than the placebo group: intensity of seborrhea (-39 % versus 33%), intensity of erythema linked to pimples (-39% versus -32%), size of dilated pores (-27% versus -26%), complexion irregularity (-37% versus -32%) , and irregularity of the relief (-37% versus -31%),
- the objective of this study is to evaluate, in vivo, the immediate effect in film form on subjects after 10 minutes of application as well as after a period of persistence of 6 hours after application, corresponding to an effect on the day.
- the active principle according to the invention in the form of a film increases the level of hydration of the skin throughout the day. In fact, immediately after application, a significant increase of 45% was observed and this effect is visible for 100% of the subjects. This level of hydration is maintained throughout the day, with a significant increase maintained at 40% in 100% of subjects after 3 hours and at 34% 6 hours after application in 94% of subjects.
- the active principle according to the invention in the form of a film, decreases the sebum of the skin throughout the day. In fact, immediately after application, a significant decrease of 51% in the sebum level was observed in 100% of the subjects. This variation is maintained throughout the day, with a significant decrease maintained at 20% in 88% of subjects after 3 hours and at 15% in 76% of subjects.
- the active principle according to the invention in the form of a film significantly improves skin hydration, while reducing the level of sebum in the skin. All of these effects are maintained throughout the day.
- the active principle according to the invention in the form of a film significantly increases the hydration of the skin by 37% in 72% of subjects after 6 applications and by 40% in 83% of subjects after 12 applications.
- the active principle according to the invention in the form of a film significantly reduces the sebum level by 22% in 83% of subjects after 6 applications and by 24% in 83% of subjects after 12 applications.
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Abstract
Description
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FR2003896A FR3109301B1 (en) | 2020-04-17 | 2020-04-17 | ACTIVE INGREDIENT COMPRISING A PARTICULAR PUNICA GRANATUM EXTRACT AND USES FOR PREVENTING AND/OR FIGHTING ACNE |
PCT/EP2021/059897 WO2021209593A1 (en) | 2020-04-17 | 2021-04-16 | Active principle comprising a peel extract of immature punica granatum fruit and uses for preventing and/or combatting acne |
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AU2012361496A1 (en) * | 2011-12-27 | 2014-07-24 | Morishita Jintan Co., Ltd. | Maillard reaction inhibitor |
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2020
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