Classifications

• • 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
  • A61Q19/08—Anti-ageing preparations
• • 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
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/92—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof
  • A61K8/922—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof of vegetable origin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
  • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
  • A61K2800/805—Corresponding aspects not provided for by any of codes A61K2800/81 - A61K2800/95
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
  • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
  • A61K2800/92—Oral administration

Definitions

• the present invention relates to an extract of whole seeds of Moringa sp. containing oil (including triglycerides, fatty acids and polar lipids) and polyphenols and its use in cosmetic and / or dermatological compositions.
• oil including triglycerides, fatty acids and polar lipids
• polyphenols and its use in cosmetic and / or dermatological compositions.
• Moringa is a tree native to India, but grown all over the world and naturalized in many environments where it is very popular. There are 13 species of Moringa belonging to the family Moringaceae, M. oleifera (synonym: Moringa pterygosperm ⁇ ) being the best known.
• Moringa oleifera is a small tree 4 to 8 meters high, with a clear crown, spread out in parasol.
• the leaves are deciduous 30 to 70 cm long, the flowers are white and very fragrant, the fruit is an elongate capsule linear, trine, leathery and pendulous, reaching 30 to 40 cm long.
• the seeds are globose-trigonal, 1.2 cm long and 1 cm wide, with 3 membranous wings exceeding the seed and 2 cm long.
• Wild or cultivated tree under tropical climate wet or very dry, it can survive in extreme conditions and has a fast growth. Its very deep roots allow it to do without water for several months.
• Ayurvedic medicine to cure 300 diseases in addition to a very important nutritional value.
• the fruits are eaten cooked, the leaves are eaten as a vegetable and have a nutritional value such that they provide a response to malnutrition in some countries.
• a high oleic food oil is derived from seeds that also serve as a flocculant to sanitize water. The oil is obtained by pressure or extraction with hexane seeds freed of their integument. For the use of the flocculant properties, the cake recovered after pressing is used.
• the seeds can be eaten like peas when they are still green. Ripe seeds contain about 40% oil.
• the oil of Moringa sp. is a good quality cooking oil (close to olive oil) also used in perfumery, for the manufacture of soap and as a lamp oil (it is very stable to oxidation).
• the oil is used in application to relieve pain during gout or rheumatism attacks (The Indian Materia Medica, pp. 811- 816). Orally, the seeds are used as antipyretic (Hukkeri et al., Indian J. Pharm Sci (2006) 68, pp 124-126).
• Oil obtained from seeds, obtained by pressing or very apolar extraction is widely used in cosmetics for its nourishing properties due to the triglycerides it contains.
• aqueous extract of seeds in cosmetics is described: the peptides and proteins it contains have anti-wrinkle and purifying properties: the seeds are previously peeled and delipidated (US 6,500,470 patents and US 2006 / 0275247).
• the aqueous and delipidated protein fractions extracted from the whole or shelled seeds of Moringa sp., Have hydrating, repairing and anti-wrinkle effects on the skin (patent EP 1 064 008).
• Said protein fraction of seeds can be characterized as "very polar".
• the seeds are composed of sterols (campesterol, stigmasterol, ⁇ -sitosterol, ⁇ 5-avenasterol, clerosterol ...), fatty acids (C18: 1-oleic-68 to 76%, C16: 0 6 to 7.8%, C18: 0 4 to 7.6%, C20: 0 2.8 to 4% and C22: 0 to 6.7%), proteins (26 to 32%), fibers, tocopherol ( ⁇ , ⁇ , ⁇ : respectively, 134, 93 and 48 mg / kg of oil).
• the seeds also contain glucosinolates including 4- ( ⁇ -L-rhamnopyranosyloxy) -benzylglucosinolate. It has also been described that the leaves and seeds of Moringa sp. contain cytokinins such as zeatin, dihydrozeatine and isopenthyladenine (US Patent 2006/0222682).
• the applicant has demonstrated the use of a specific extract of whole seeds of Moringa sp. comprising oil (including triglycerides, fatty acids and polar lipids) and polyphenols as active ingredient in cosmetic and / or dermatological compositions.
• oil including triglycerides, fatty acids and polar lipids
• polyphenols as active ingredient in cosmetic and / or dermatological compositions.
• the present invention thus relates to an extract of whole seeds of Moringa sp. containing oil (including triglycerides, fatty acids and polar lipids) and polyphenols.
• oil including triglycerides, fatty acids and polar lipids
• polyphenols including triglycerides, fatty acids and polar lipids
• whole seeds is intended to mean seeds which have not been freed of their integument.
• an oil content of 5% to 50% including (i) 2% to 10% of triglycerides and fatty acids and (ii) 5% to 15% of polar lipids; and a content of total polyphenols of 0.01% to 5% (expressed as g of pyrogallol per 100 g of solids).
• said extract has an oil content of 25% to 40% (% by weight relative to the weight of the dry extract).
• the species of Moringa is preferably Moringa oleifera or Moringa drouhardii.
• Said extract of Moringa sp. according to the present invention is obtained from whole seeds of Moringa sp., advantageously dried, crushed and then subjected to at least one extraction with a medium polar solvent.
• the term "medium polar solvent” is intended to mean a solvent chosen from the group consisting of a C 1 to C 4 alcohol, acetone, a water / alcohol mixture and an acetone / acetone mixture. water, used alone or in mixtures.
• this ethanol / water mixture will be characterized by various ethanol / water proportions of 9/1 to 7/3 (v / v).
• the medium polar solvent is an ethanol / water mixture of 9/1 or 3/1 (v / v).
• the extraction is carried out with stirring or in a static manner, at reflux or at ambient temperature, in a ratio plant weight / solvent volume that can vary from 1/5 to 1/20, for a period of 30 minutes to 48 hours.
• the extraction can be renewed 2 or 3 times.
• the marc is then separated from the extract by centrifugation or filtration and the solution may be more or less concentrated until a solids content is obtained with yields ranging from 5% to 10%.
• a support may be added during the drying step in proportions by weight relative to the dry matter extracted, which may vary from 1% to 75%.
• the support may be maltodextrin, lactose, silica or any other cosmetologically acceptable carrier and solubilizing the extract, such as, for example, the propylene glycol / oleic alcohol mixture ethoxylated in various proportions.
• the extract of Moringa sp. obtained is characterized by its oil content (including triglycerides, fatty acids and polar lipids) and polyphenols.
• Another subject of the present invention relates to such an extract of Moringa sp. for its use as an anti-aging active ingredient.
• said extract is intended to combat all the signs of skin aging in people with mature skin.
• the term "mature skin” is intended to mean the skin of persons who are typically over 55 years old and more preferably over 60 years old.
• the marks of aging of the skin result in particular in a loss of firmness and / or elasticity and / or tonicity and / or suppleness of the skin and the formation of wrinkles and fine lines.
• the object of the present invention is therefore to provide a new active capable of providing both protection, hydration and nutrition to the epidermis / mature skin, and consequently to give the skin smoothing effects. , anti-loosening, restructuring.
• the Applicant has evaluated the overall anti-aging action of extracts of Moringa sp. according to the present invention.
• the extract according to the present invention promotes hydration, smoothing, non-loosening, and restructuring of the skin.
• the extract according to the present invention thus makes it possible to embellish and unify the skin complexion.
• Another object of the present invention is the use of an extract as defined to enhance and restore the barrier function of the skin.
• the expression "reinforcing the barrier function of the skin” means improving the barrier function of the skin.
• One of the fundamental functions of the skin is to provide a barrier between the body and the external environment, opposing in a sense the penetration into the epidermis of fungi, bacteria and allergens of the environment ("outside-in” ) and in the other direction to the water loss (“inside-out”).
• the epidermis is a pluristratified epithelium, of ectodermal origin, in perpetual renewal.
• the basal layer There are several layers of different morphological and cellular composition, from the inside to the outside: the basal layer, a cell base whose keratinocytes have a very strong proliferation capacity which allows the self-renewal of the epidermis then the suprabasal layers (the granular, thorny layers) and finally the stratum corneum (Stratum Corneum, SC). These stages correspond to more and more advanced levels of keratinocyte differentiation.
• the keratinocytes of the basal layer lose their capacity for proliferation as soon as they enter a process of migration towards the surface of the epidermis, during which the keratinocytes will express a program of differentiation leading to the cornification, a process of programmed cell death.
• the cutaneous barrier function is ensured in the first place by the stratum corneum, a solid and tight assembly formed of two compartments: - a lipid-rich intercorneocyte cement: the lipids, organized in layers and covalently linked to the cells, limit the penetration of the molecules through the stratum corneum;
• cornified cells dead and devoid of organelles (corneocytes), which correspond to the final stage of the keratinocyte differentiation.
• the integrity of the extracellular lipid cement as well as all the cellular elements of the stratum corneum and the balance between keratinocyte proliferation and differentiation are essential for maintaining a functional epidermal barrier function.
• the disruption of the barrier function makes the body sensitive to external aggression and dehydration.
• the improvement of the barrier function is crucial when the barrier function of the skin is impaired and it is necessary to restore it. This is the case in a certain number of physiological states, in response to time (skin aging) or in connection with the hormonal context or stress. The speed of this restoration allowing the return to homeostasis is delayed.
• the cutaneous barrier function is impaired in the majority of the most common skin conditions in the population that are often accompanied by an inflammatory component (dry skin ).
• the improvement of the barrier function may also be advantageous when it is desired to consolidate the native function of the skin, in order to confer in particular on the body a better resistance to the external aggressions against which it is likely to be exposed, in particular Environmental type (Ultraviolet, humidity, outdoor temperature, pollution, burns).
• the barrier function of the skin includes all the mechanisms of natural defense against the aggressions to which it is subject. The essential element providing this function is located in the most superficial part of the epidermis, at the level of the stratum corneum, called the stratum corneum.
• the use of the extract according to the present invention is particularly effective for strengthening and restoring the cutaneous barrier function.
• Another subject of the present invention relates to a cosmetic and / or dermatological composition
• a cosmetic and / or dermatological composition comprising, as active ingredient, an extract of whole seeds of Moringa sp. according to the invention and at least one cosmetologically and / or dermatologically acceptable excipient.
• Said cosmetic and / or dermatological composition according to the present invention comprises a quantity of dry extract of whole seeds of Moringa sp. between 0.1 g and 5 g per 100 g of said composition.
• said amount of Moringa sp. is between 0.25 g and 1 g per 100 g of cosmetic and / or dermatological composition.
• the invention relates to an anti-aging cosmetic composition.
• said cosmetic composition is intended to combat all the signs of skin aging in people with mature skin.
• the anti-aging cosmetic composition according to the present invention may contain, in addition, one or more other active ingredients such as active agents for sunscreen and / or skin depigmenting active agents.
• the active ingredients for sun protection are furthermore chosen from among chemical synthesis molecules known for their anti-UVA action, for their anti-UVB action such as octocrylene and / or dioctyl butamido triazone and / or bis-ethylhexyloxyphenyl. methoxyphenyl triazine
• the active agents for depigmentation of the skin, to lighten and even out the complexion may be, in addition, niacinamide, vitamin C and its derivatives.
• the cosmetologically acceptable excipient for obtaining an anti-aging cosmetic composition is chosen to allow topical or oral administration.
• the topical form is chosen from the group consisting of a milk, a cream, a balm, an oil, a lotion, a gel, a foaming gel, a ointment, spray, etc.
• the oral form is chosen from the group consisting of tablets, capsules, lozenges, powder, granules, solutions or oral suspensions.
• the invention also relates to a cosmetic and / or dermatological composition intended to strengthen and restore the barrier function of the skin.
• the cosmetologically and / or dermato logically acceptable excipient for obtaining a cosmetic and / or dermatological composition reinforcing and restoring the barrier function of the skin is chosen to allow topical administration.
• the topical form is chosen from the group consisting of a milk, a cream, a balm, an oil, a lotion, a gel, a foaming gel, a ointment, spray, etc.
• Another subject of the present invention relates to a cosmetic process for combating all the signs of cutaneous aging in persons with mature skin, characterized in that it involves the use, topically or orally, of an extract of whole seeds of Moringa sp. according to the invention.
• Example 3 20 g of dried and ground Moringa drouhardii whole seeds are extracted with 200 ml of 90:10 ethanol / water at reflux for 1 hour. The extracted solution is recovered by solid / liquid separation and dried on a rotary evaporator at 50 ° C. 1.29 g of extract are thus obtained in the form of a yellow-brown paste titrating at 35% of oil (triglycerides fatty acids and polar lipids) and 1.3% of total polyphenols expressed as pyrogallol.
• oil triglycerides fatty acids and polar lipids
• Siloxane (cytclopenta) decamethyl 1 to 8 g Glycerine 99.5% 1 to 5 g
• the antioxidant activity of the Moringa oleifera seed extract according to the present invention was evaluated with the DPPH test. This test is based on the measurement of the antioxidant trapping capacity of the stable 2,2-diphenyl-1-picrylhydrazyl radical.
• Results The results obtained are expressed as IC50, corresponding to the concentration giving 50% reduction in the absorbance of a methanolic solution of DPPH at 0.06 mM.
• the extract according to the invention has an antioxidant activity mainly provided by the molecules present in the integument.
• Results 65 ⁇ g of extract according to Example 1 are necessary to obtain an activity equivalent to the activity detected for 1 ⁇ g of trolox: activity equivalent to lycopene, a molecule known for its antioxidant activity.
• the epidermis plays a major protective role in providing a chemical and mechanical barrier for the body. It ensures the maintenance of the seal, namely the skin barrier function. Corneocytes, keratinocytes of the stratum corneum, associated with a lipid matrix, largely ensure this function. Nevertheless the deeper layers intervene in the setting up of the actors of this function. The differentiation capacity of the keratinocytes of the epidermis will guarantee the establishment of a functional selective permeability barrier (Elias PM, J Invest Dermatol 125 183-200 (2005)).
• epidermal differentiation is mainly focused on the evolution of structural proteins that are keratins and that contribute to the architectural integrity of the epidermis. Their expression varies according to the degree of maturation of the keratinocytes.
• Basic keratin 1 and acidic keratin 1 are early markers of keratinocyte differentiation present in the basal layer of the epidermis.
• transglutaminases such as transglutaminase 1 (TG1) (Houben E, et al., Skin Pharmacol Physiol, 20 (3): 122-32 (2007)).
• keratinocyte lipids are at the origin of the intercorneocyte lipid cement essential for the cutaneous barrier, the formation of which represents the final phase of epidermal terminal differentiation.
• This extracellular lipid matrix provides the main barrier to transcutaneous movements of water and electrolytes Mizutani Y., et al. FEBS Lett. 563: 93 (2004))
• a number of enzymes and lipid transporters see their keratinocyte expression increase with differentiation.
• certain members of the ABC (Adenosine Triphosphate Binding Cassette transporter) family play a major role in the steps of lipid barrier implantation.
• ABC Gl which carries glycerol specifically
• ABC A12 essential for the transfer of lipid precursors in the lamellar bodies
• Epidermal ceramides play a major specific role and represent an essential marker of the level of functionality of the skin barrier.
• enzymes involved in the synthesis of cutaneous ceramides see their expression and their activity specifically increased during a rupture of the epidermal barrier function and with the level of epidermal differentiation. This is the case in particular of Sphingolipid C4-hydroxylase / delta-4 desaturase or hDES2 whose dihydroceramide hydroxylase activity contributes to the synthesis of cutaneous phytoceramides in humans (Feingold, KR J Lipid Res 48: 2531-2546 ( 2007)).
• results are expressed as a percentage of stimulation of the gene expression (mRNA) of different markers of epidermal differentiation expressed by NHKs (compared to untreated cells). A significant positive effect is considered from 100% stimulation.
• the results obtained are shown in the table below.
• Table 1 Effect of vitamin D3, roziglitazone and the extract according to the invention from a model of differentiated normal human keratinocytes (NHK).
• the extract prepared according to Example 1 at 20 ⁇ g / ml induces the gene expression of hDES2 and ABC Gl.
• the extract prepared according to Example 1 makes it possible to restore the lipidic epidermal differentiation at the origin of the establishment of the hydrophobic barrier making it possible to limit skin dehydration, which is particularly encountered in mature skin.
• the extract according to Example 1, at 1 and 10 ⁇ g / ml makes it possible to restore the expression of Kl (11 and 35% respectively) and involucrine (15% for 10 ⁇ g / ml).
• Extracellular matrix is a dynamic structure with a structural and regulatory role for tissues. It gives the skin its turgidity and its mechanical properties: firmness, elasticity and tone. At the level of the epidermis it occupies the intercellular space and plays a role of maintenance for the epidermal edifice. It also exchanges between cells of the epidermis and plays a role in cell activity.
• the ECM of the epidermis consists in particular of collagen (fibrous protein) type IV. When a cell is senescent, the components of the ECM are mainly degraded by enzymes of the zinc endopeptidase type called matrix metalloproteinases or MMPs.
• MMP-9 is a gelatinase that has activity against denatured collagen molecules (gelatin) but can also cleave native molecules of type IV, V and VII collagen.
• the extract prepared according to Example 1 inhibits the gene expression of MMP-9 at 1, 10 and 30 ⁇ g / ml, and this significantly at the three concentrations.
• the extract prepared according to Example 1 makes it possible to restore the mechanical properties of the MEK: firmness, elasticity and tone of the ECM of the skin and also makes it possible to restore the protein structure of the epidermis.

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