JP2009029806A - Use of fat-soluble extract of odontella aurita for restructuring skin, composition for use and cosmetic method using the extract - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To use for cosmetic, in a composition, at least one fat-soluble extract of Odontella aurita, so as to restructure the skin or to evade its deterioration. <P>SOLUTION: New formulations comprising, as the active component, a natural fat-soluble extract of Odontella aurita, associated with a cosmetic or dermatologically appropriate transdarmal nano-colloid type vehicle, are provided. Also, a cosmetic care method for coping with skin ageing or deterioration of the skin and/or for restructuring the skin, is provided. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to the use of a fat-soluble extract of the diatom Odontella Aurita in cosmetic compositions as a skin reconstituting agent, in particular as an anti-aging agent.

  Skin is a collection of cells that accumulate in the form of tough, flexible tissue that covers the entire body. Its first function establishes a protective barrier against environmental attacks while allowing an exchange between internal and external media. It is the location of many metabolic processes controlled by the physiological and environmental conditions of the organ. The skin is formed by two types of connective layers, the epidermis and the dermis, to which subcutaneous tissue will be attached.

  The epidermis functions primarily to protect the body and constitutes the outermost layer of the skin, providing impermeable and toughness to the skin. It renews itself every 4 weeks. Various types of cells coexist in the epidermis; keratinocytes are the majority (90%). Their characteristic activity is the synthesis of keratin, which accounts for 95% of the total protein of the epidermis. Keratin is a fibrous protein that is insoluble in water and is a component of the stratum corneum of the epidermis, which protects the skin against external attacks such as heat, cold, dehydration and the like.

  The epidermis is connected to the dermis through a region called the dermal epidermal junction or epidermal basement membrane. This structure serves as a mechanical adjunct that binds the dermis to the epidermis and is partly responsible for skin tonus. It contains both basal keratinocytes and dermal fibroblasts, and contains large amounts of type 4 collagen associated with anchored plaques that bind the basement membrane to anchoring plaques present in the dermal papillary layer.

  The inner layer of the dermis and skin is a fibro-elastic conjunctive tissue composed of cells and fibroblasts dispersed in a composite medium called an extracellular matrix. This matrix is composed of proteoglycans formed by collagen and elastic fibers, glycoproteins, ie fibronectin and laminin, and a central protein to which glucosaminoglycans or GAGS are added.

  The nature and amount of these various components determines the mechanical properties of the skin and is responsible for the most visible physiopathological changes to the skin profile that can be observed during aging. The fibers impart firmness, toughness, elasticity, and tension to the skin. Glycoproteins and proteoglycans give volume and are involved in hydration.

  Collagen, especially type 1 and type 3 fibrillar collagen proteins that make up 75% of the dermis, form a fibrous network of dermis. They play a mechanical role by giving the skin most of the support and elasticity. Due to their specific spatial arrangement, some rigidity is imparted to the structure of the dermis, thus contributing to their mechanical function. They are derived from procollagen, a precursor synthesized by fibroblasts.

  Proteoglycans that are distributed among the fibers of the dermal connective tissue impart most of the skin tension. Their structures (polymers formed by glycosaminoglycans and long chains of polysaccharides) give proteoglycans a negative charge that traps ions, water, and various metabolites, thereby hydrating the skin, and pressure And contributes mainly to resistance to pulling force.

  During aging, skin wrinkles, slacken, are less hydrated and more difficult to repair themselves. These clinical signs affect the appearance or cause skin disease, but are essentially extrinsic processes due to the action of ultraviolet light and attack by environmental factors such as contamination, as well as actual life starting at age 20 It is the result of superposition of endogenous processes corresponding to aging.

  Aging initially affects the epidermis. The splitting power of keratinocytes in the basal layer decreases, and the regeneration time of the surface stratum corneum increases. This decrease in epithelial cell division power also results in a decrease in the enzyme (SIR2) group involved in “cell longevity”, particularly the enzyme SIRT1.

  Cell maturation is incomplete and keratinization can no longer produce an orderly and uniform stratum corneum, resulting in a decrease in epidermal thickness, which becomes dry and rough in appearance. At the same time, the deep part of the skin becomes less organized. The dermis imparts the basic functions of skin binding and nutrition and is a major target for skin damage. In senescence, fibroblasts are a source of constitutive substrate for skin, but disappear or transform into fibrocytes. As a result, a decrease in the amount of fibronectin is observed. Fibronectin plays a major role in adhesion and cell function, and in reducing the number and quality of elastic fibers.

  Decreased quality of collagen, 1% per year, glycosaminoglycan, and the major inhibitor of metalloproteinase responsible for dermal degradation, loss of dermal elasticity and reduced skin thickness Is explained.

  The loss of the flexibility of the connection that connects the dermal cells together is the cause of various bruises and lacerations that can be observed in the elderly. This also explains the appearance of wrinkles on the bags under the eyes and on the skin, as well as the dermal damage that was noticeable during minor trauma.

  The long lifespan associated with the desire to retain a young appearance has stimulated studies to understand that the structure of the skin changes during aging. The appearance of wrinkles and fine lines is mainly due to the structural tissues of the skin, ie, connective, horny, and fibroblast tissues. Of those components, collagen, elastin, and keratin all play an essential role in cosmetic modifications to the skin. Anti-aging cosmetic products act on some of these. There are numerous facial “lifting” treatments and programs on the market aimed at reducing wrinkles and improving skin elasticity. These usually act on the skin surface, or only one of the target proteins mentioned above; their effects are provisional and partially satisfactory. Furthermore, many of the applied compounds are not completely non-toxic and their habitual application may cause the appearance of skin problems such as inflammation. They are often produced using chemical synthesis or extraction from both natural and time consuming and expensive substrates.

For these reasons, there is a need for compounds or compositions that do not have the disadvantages described above, that is, are non-toxic, easy to obtain, and act on multiple protein targets simultaneously. .
French patent document FR-A-2 795958 P Ganter and G Jolles, "HIstochimie normale et pathologue" [Normal and pathological Histochemistry], published by Gautier Villars (1970) M Dowsett, "Effect of raloxafene on breast cancer cells-Ki67 apoptosis", Cancer Epidemiology Biomarkers publication, September (2001) Jean Chevreau, Jacqueline Bellot and Marie-Jose Cabanier "Formularie de techniques histologiques" [Formulary of histological techniques], published by Maloine (1956) Fyrand O, "Studies on fibronectin in the skin. III Indirect immunofluorescence studies in lichen planus", Acta Derm Venereol (1979); 59 (6): 687-92 Dal Farra C and Domloge N, "SIRT1, the human homologue to Sir 2 etc", Soc Cosm Chem Annual Sci Meeting (2005), 65-66

  Surprisingly, Applicants have shown that the fat-soluble extract of Odontera Aurita can act simultaneously on multiple of these targets in both the dermis and epidermis, resulting in multiple levels of action simultaneously. I found Such extracts also have the advantage of being easy to isolate and easy to use. Furthermore, due to their nature, ie those that are fat-soluble that are rich in certain sterols, such extracts have very low or no toxicity to the organism.

  Lipid extracts from Odonterra Aurita are known (CTFA 12540) and are described in French patent document FR-A-2 795958 for use in the field of treating obesity.

  The present invention therefore relates to the cosmetic use of at least one fat-soluble extract of Odontera Aurita as a medicament for reconstituting the skin or avoiding its destructuring.

  In particular, the present invention prevents, reduces and / or counteracts the intrinsic or extrinsic aging of the skin and in particular improves the elasticity or tension of the skin and / or the appearance of skin wrinkles or fine lines. It relates to the use of a fat-soluble extract of Odonterra aurita in a composition as a drug to overcome.

  In a further aspect, the present invention uses a fat-soluble extract of Odontera Aurita to regenerate or improve skin regeneration after dermabrasion, chemical exfoliation, or laser trsurfacing. Related to doing.

  More precisely, the present invention relates to the use of a fat-soluble extract of Odontera Aurita to improve and / or stimulate the synthesis of procollagen, fibronectin, glycosaminoglycan, and / or SIRT1. To do.

  The invention further relates to a cosmetic or dermatological composition comprising a fat-soluble extract of Odonterra aurita and a transdermal vector vehicle. The transdermal vector vehicle is of the nanocolloid or nanoparticle type, preferably the nanocolloid type. Examples of nanocolloid transdermal vectors that can be cited are nanoemulsions, liposomes, and cyclodextrins.

  Finally, the invention also relates to a cosmetic method for the care and / or treatment and / or prevention of skin aging or skin structure destruction, in which method at least one fat-soluble extract of Odontera Aurita And a cosmetically acceptable vehicle is applied to the skin. Preferably, the lipid extract of Odonterra Aurita is present in the vehicle in the form of a nanocolloid.

  As will become clearer from the following detailed description, in particular from the following formulation examples and examples, the use of a fat-soluble extract of Odontera Aurita, or a cosmetic composition comprising such an extract, is Can be stimulated, resulting in an increase in the number of viable cell layers in the treated explant and an increase in the thickness of the epidermis.

  Furthermore, by using the lipophilic extract according to the application of the present invention in a detailed test to measure the mitotic index or the expression of GAG, fibronectin or sirtuin, positive results, i.e. increased mitotic index over the control Or, in the dermal papilla layer, particularly in the rows present along the dermal epidermal junction, and in the increase of GAG in fibroblasts, and high concentrations of SIRT1 and fibronectin in the biopsy of the treated skin. This means that the epidermis and dermis may have been reconstituted under the action of the fat-soluble extract of Odonterra Aurita.

  According to the present invention, any fat-soluble extract of Odonterra aurita that is cyanobacteria, microalgae, or plankton can be used. The collected plankton is processed in the usual way to obtain a fat-soluble extract.

  These fat-soluble extracts of Odonterra aurita may be obtained using traditional extraction methods involving, for example, organic solvents such as hexane or dichloromethane. However, any method that can extract the lipid phase of Odontera aurita or any method for extracting a fat soluble extract from this plankton can be used. French Patent Document FR-A-2 795958 describes an extraction method using a supercritical fluid such as carbon dioxide. Finally, Odonterra Aurita oil can be purchased from Codif.

  These lipid extracts are fat soluble. Other fat-soluble extracts in any oil or silicone oil or other cosmetically acceptable fat-soluble substrate are suitable for use in the present invention.

  The fat-soluble extract of Odontera Aurita is in the range of 0.001% to 50% by weight, preferably in the range of 0.5% to 20% by weight, more preferably 0.1% to 10% by weight relative to the total weight of the composition. Present in the composition used to practice the present invention in an amount in the range of%.

  The term “transdermal vector vehicle” means, in the present invention, any vehicle that is capable of allowing the extract to penetrate the skin.

  The term “nanocolloid” means a nano-sized, monodisperse, non-solid form that is smaller than about 200 nm. Nanocolloids usually contain nanoemulsions (surfactant monolayers), but form liposomes or inclusion complexes that are small in size (at least one layer of a natural phospholipid type surfactant). Cargo molecules such as α-, β-, or γ-cyclodextrin may also be included.

  The cosmetic compositions used according to the invention are intended for topical use and are in any of the formulation forms in traditional use for this type of application, in particular oil-in-water emulsion O / W, water-in-oil emulsion W. / O, an oil-in-water-in-oil triple emulsion O / W / O, or a water-in-oil-in-water emulsion W / O / W, an aqueous gel, or an aqueous, aqueous alcohol, or oily solution. They are more or less liquid and may be white or colored cream, pomade, milk, lotion, serum, paste, foam, or two-phase liquid. Thus, transdermal vectors may include O / W, W / O, W / O / W, O / W / O emulsions, gels or fat-soluble liquids. They can also be in solid form, for example in the form of a stick or in the form of an aerosol.

  In addition to the fat-soluble Odontera Aurita, the composition used in the present invention comprises one or more excipients, which may be selected from compounds that have good compatibility with the active ingredients present in the chemical formula. Including. Examples are polysaccharides (xanthan gum, carouba gum, peptin, etc.) or natural water-soluble polymers such as polypeptides, methylcellulose-type cellulose derivatives, hydroxypropylcellulose, hydroxypropylmethylcellulose or synthetic polymers, poloxamers (poloxamer), carbomer, or polyvinyl acrylate (PVA) or polyvinyl pyrrolidone (PVP) type gelling agent.

  Finally, the compositions of the present invention can also be used in various other co-solvent type excipients such as ethanol, glycerol, benzyl alcohol, humectants such as glycerol, diffusion aids such as urea, A microbial preservative may also be included, such as 0.15% methyl p-hydroxybenzoate.

  They also include surfactants, stabilizers, emulsifiers, thickeners, other active principles that produce complementary or possible synergistic effects, oligo-elements, essential oils, fragrances, colorants , Collagen, chemical or inorganic filter agents, humectants, or hot springs may also be included.

  The Odonterra aurita extract may be combined with at least one other active, such as a wettable powder.

  The method of the present invention can be applied in a conventional manner by topical application of the composition to be applied, e.g., daily, twice a day, or every time the skin is washed, or after skin peeling, chemical peeling, and laser beautification. Performed intensively.

  The method is applicable to all skins: the compositions of the present invention may be applied to the face, but can also be provided to apply them to other parts of the body; It may vary depending on the situation and / or may be specific to a certain region.

  The following examples illustrate the invention without limiting the scope of the invention in any way.

<Measurement of activity>
<Reconstitution of preparation containing fat-soluble extract of Odontera aurita and research on anti-aging activity>
The study was performed on 36 explants from human skin obtained from abdominal skin cosmetic surgery performed on a 49-year-old woman.

  All explants were kept alive in the culture medium for 4 days. 30 μl of Odontera Aurita lipid extract diluted in an oily solvent (caprylic acid capric acid triglyceride, “Myritol 318 Neutral Oil” from GOGNIS) and placed on the surface of sterile paper, topically and daily Added to the graft. On the 0th and 4th day of treatment (D0 and D4), 3 explants were removed from each batch (control, 10% lipid extract, 1% lipid extract) for anatomical studies Prepared. A rough description of the morphology, mitotic index, and evaluation of the expression of glycosaminoglycans without acid groups were carried out with the following results.

I. Rough form
Observations were made using the method described in “HIstochimie normale et pathologue” [Normal and pathological Histochemistry] by P Ganter and G Jolles, published by Gautier Villars (1970). Epidermis, which observes all explants and results in an increase in the number of viable cell layers from application of two diluted concentrations of Odontera Aurita's diluted lipid extract from day 4 of treatment. Structural stimulation was induced. The increase in epidermal thickness was greater according to the application of Odontera Aurita 10% lipid extract.

II. Splitting index
The mitotic index was measured using the method described in M Dowsett, “Effect of raloxafene on breast cancer cells-Ki67 apoptosis”, Cancer Epidemiology Biomarkers publication, September (2001).

  In biopsy sections, mitotic cells were labeled with anti-Ki67, monoclonal antibody clone 7B11, mouse IgG1. Labeling was performed on frozen sections after fixation in acetone. Anti-Ki67 was diluted 1/100 in PBS and added for 2 hours at room temperature. It was revealed using the Vectastatin RTU universal vector reveiling kit, reference PK-7200. It was visualized by an optical microscope with a 40 × objective, and the results averaged the center of the epidermis length.

  Anti-Ki67 labels G1, S, G2, and M phase cells.

  As can be seen in Table 1, the mitotic index observed at D4 in biopsies from skin treated with Odontera aurita lipid extract is higher than that obtained with untreated control and extract dilution solvent Had a value. These values increased as a function of extract dose.

III. Expression of glycosaminoglycan (GAG)
The expression of GAG was studied using the method described in Jean Chevreau, Jacqueline Bellot and Marie-Jose Cabanier "Formularie de techniques histologiques" [Formulary of histological techniques], Maloine publication (1956).

  Anatomical sections from skin explants are stained with Alcian blue PAS specific for GAG without acid groups, Odontera Aurita lipid extract and explants at two test concentrations After treatment, it was shown that these GAG components in the skin were significantly increased. This effect is clearly seen in D4, but by increasing the number of fibroblasts that are clearly PAS positive in the dermal papilla layer, particularly in the rows located along the dermal epidermal junction, or these Characterized by an increase in GAG in fibroblasts.

IV. Expression of fibronectin and sirtuin (SIRT1) To detect fibronectin, Fyrand O, "Studies on fibronectin in the skin. III Indirect immunofluorescence studies in lichen planus", Acta Derm Venereol (1979); 59 (6): 687 -92, and the method described in Dal Farra C and Domloge N, "SIRT1, the human homologue to Sir 2 etc", Soc Cosm Chem Annual Sci Meeting (2005), 65-66, to detect SIRT1 Thus, the expression of fibronectin and sirtuin (SIRT1) was evaluated.

  Biopsy from skin treated with solvent or untreated controls in biopsy sections from skin treated with lipid extract of Odonterra aurita at D4 by labeling with specific anti-SIRT1 and anti-fibronectin antibodies These SIRT1 and fibronectin molecules were shown to be highly concentrated compared to the skin of

<Conclusion>
The above observations show remodeling of the epidermis and dermis by the action of the lipid extract of Odonterra Aurita.

  This type of modification represents a criterion for younger or rejuvenating skin.

<Formulation example>
The following formulations were prepared by methods standard to those skilled in the art. In Formulation Examples 1 to 4, after heating to 80 ° C., the aqueous phase and the fatty phase were usually mixed with vigorous stirring to emulsify them.

  Odontera Aurita's lipid extract was supplied by Codif.

<Formulation Example 1: Reconstitution cream for aging skin>

<Formulation Example 2: Moisturizing cream intended for normal skin>

Formulation Example 3: Creams and emulsions intended for aged skin exposed to sunlight>

<Formulation Example 4: Wrinkle prevention cream>

<Formulation Example 5: Makeup Removal Lotion for Mature Skin>

<Formulation Example 6: Regenerated oil for skin that is easily damaged and suffers from denutrition>

<Formulation Example 7: Odonterra Aurita Nanocolloid Anti-aging Serum>
-1- Preparation of nano colloid of Odontera aurita lipid extract:
Odontera Aurita lipid extract dissolved at 10% in oil (Myritol 318-caprylic acid capric acid triglyceride) is a vegetable grade oil-based emulsifier (Axol C62-from Degussa) with an HLB value of 12. Glyceryl stearate citrate). The ratio of the emulsifier to the fatty phase was 0.1. A seawater / mineral water phase (marine spring water from SOMAIG, IleGrade) diluted 1/4 in mineral water (Source Ste Alix, Brittany) contained 10% glycol and 0.1% sodium ascorbate.

  It was produced as follows. The emulsifier was diffused into the hot water phase using a rotor / stator (RAYNERI VMI TURBOTEST) for 3 minutes. This first mixture was homogenized with 1 pass (Lab 1000, APV) at high pressure: 700 bar. It was allowed to cool to room temperature. Additives, and heat sensitive fat soluble extract of Odonterra Aurita were added and homogenized using a rotor / stator. The mixture was homogenized again at high pressure (700 bar, 1 pass).

  Particle size and monodispersity were confirmed using a light scattering technique (MASTERSIZER HYDRO 2000S, MALVERN INSTRUMENTS laser granulometer).

  The particle size was 200 nm.

＜実施例＞
オドンテラ・アウリタナノコロイド老化防止セラムのヒトにおける活性の研究
研究は15人（30歳から60歳）の2群に対して実行した。
・プラセーボ、配合例７(-2-)のオドンテラ・アウリタナノコロイドセラム賦形剤を、朝晩49日間中断なく使用する一群（平均年齢：41歳）；
・配合例７(-2-)のオドンテラ・アウリタナノコロイド老化防止セラムを、朝晩49日間中断なく使用する一群（平均年齢：45歳）。 -2- Odonterra Aurita Nanocolloid Anti-aging Serum Composition

<Example>
Study of human activity of Odontera Aurita nanocolloid anti-aging serum The study was conducted on two groups of 15 people (30 to 60 years old).
-Placebo, a group (average age: 41 years old) of Odontera Aurita Nanocolloid Serum Excipient of Formulation Example 7 (-2-) used without interruption for 49 days in the morning and evening;
A group (average age: 45 years old) that uses the odonterra aurita nanocolloid anti-aging serum of Formulation Example 7 (-2-) for 49 days in the morning and evening without interruption.

  At the end of the process, a questionnaire was conducted to people.

  The answers obtained are shown in% in Table 2 below.

Claims (12)

  Use of a fat-soluble extract of Odontera Aurita as a medicament for reconstituting the skin or preventing structural destruction of the skin.   Use according to claim 1 as a medicament against endogenous or extrinsic skin aging.   Use according to claim 1 or 2 to improve skin elasticity and / or tension and / or to prevent, reduce and / or stop the appearance of skin wrinkles or fine lines.   Use according to claim 1 for improving skin regeneration after skin peeling, chemical peeling or laser beautification.   Use according to any one of claims 1 to 4, for improving and / or stimulating the synthesis of procollagen, fibronectin, glycosaminoglycan and / or SIRT1.   A cosmetic or dermatological composition comprising a fat-soluble extract of Odontera Aurita and a nanocolloid transdermal vector vehicle.   The cosmetic or dermatological composition according to claim 6, comprising a fat-soluble extract of Odonterra aurita and a nanoemulsion-type transdermal vector vehicle.   The cosmetic composition or dermatological composition according to claim 6, comprising a fat-soluble extract of Odontera aurita and a liposome-type transdermal vector.   The cosmetic composition or dermatological composition according to claim 6 or 7, comprising a fat-soluble extract of Odonterra aurita and a cyclodextrin type transdermal vector.   The transdermal vector is a water-in-oil (W / O), oil-in-water (O / W), water-in-oil-in-water (W / O / W), or oil-in-water-in-oil (O / W / O) emulsion, gel, Alternatively, the cosmetic composition or dermatological composition according to any one of claims 6 to 9, comprising a fat-soluble liquid.   The fat-soluble extract of Odonterra Aurita is in the range of 0.01% to 10% by weight, preferably in the range of 0.05% to 5% by weight, more preferably 0.1% to 2% by weight relative to the total weight of the composition. 11. A cosmetic or dermatological composition according to any one of claims 6 to 10 present in an amount in the range of%.   A cosmetic composition comprising at least one Odontera aurita fat-soluble extract and a cosmetically acceptable vehicle is applied to the skin to care for and / or treat skin aging or skin structure destruction Beauty methods for, and / or preventing.