Cosmetic or pharmaceutical compositions comprising at least hyaluronic acid, Kakadu plum extract and thermal water from the Herculane spring.
A synergistic blend of hyaluronic acid, Kakadu plum extract, and Herculane spring water addresses skin aging by stimulating collagen and hyaluronic acid synthesis, improving skin structure and reducing inflammation, resulting in a youthful appearance.
Patent Information
- Application Number
- FR2023003588
- Authority / Receiving Office
- FR · FR
- Patent Type
- Patents
- Current Assignee / Owner
- Filing Date
- 2023-04-11
- Publication Date
- 2026-01-30
- Estimated Expiration
- 2043-04-11
AI Technical Summary
Existing cosmetic compositions fail to provide a lasting effect on signs of aging and do not effectively restore or improve the skin's structure, cohesion, and reduce chronic inflammation.
A cosmetic or pharmaceutical composition comprising hyaluronic acid with a molecular weight between 10 and 60 kDa, Kakadu plum extract, and thermal water from the Herculane spring, synergistically working to reduce signs of aging by stimulating collagen and hyaluronic acid synthesis, reducing inflammation, and protecting dermal and epidermal elements.
The composition visibly and durably reduces wrinkles, improves skin appearance by enhancing elasticity, firmness, and hydration, while reducing chronic inflammation.
Abstract
Description
Title of the invention: Cosmetic or pharmaceutical compositions comprising at least hyaluronic acid, Kakadu plum extract and thermal water from the Herculane spring. FIELD OF INVENTION
[0001] The present invention relates to the preparation of cosmetic or pharmaceutical compositions having an anti-aging effect. STATE OF THE ART
[0002] Aging, particularly skin aging, is a multifactorial phenomenon. One example is the harmful action of free radicals, especially oxygen radicals, on the skin's structure and metabolism. These oxygen radical species can also form in the skin through the action of solar radiation (and more specifically UV rays), air pollution, or inflammatory processes such as fever or the use of certain medications. These reactive oxygen species can also have an endogenous origin: indeed, cellular respiration by mitochondria produces free radicals that are toxic to the unsaturated fatty acids of cell walls (oxidized fatty acids are no longer available for various important metabolic processes), toxic to structural proteins (collagen, elastin) leading to their stiffening, toxic to enzymes by denaturing them and thus inactivating them, and finally toxic to DNA where they can produce mutations that can either inactivate protein production or produce non-conforming proteins, sometimes deviant ones such as certain oncogenes (Borel 1984, Buechter 1988). It is known that in human cells, the amount of oxidized proteins increases exponentially with age.
[0003] Oxygen radical species produced in the skin by exposure to light, whether solar or artificial, produce the same damage. It is known that, in particular, type A UV radiation penetrates quite deeply into the skin, reaching the dermis, which is then subjected to this degradation.
[0004] The skin is not without possibilities to fight against these phenomena, in particular by producing enzymes such as SuperOxyDismutase, Catalase, Glutathione peroxidase or heme-oxygenase-1 or 2, and by mobilizing Vitamin C and Vitamin E from the bloodstream.
[0005] But these internal protections can be overwhelmed in the event of severe aggression, weakening of the body, fatigue, taking certain medications, triggering a deleterious cycle of aging, in particular by maintaining low-grade chronic inflammation.
[0006] To try to break this harmful cycle, the skin can be supplemented with Vitamin C through exogenous administration. This has long been a widespread practice in cosmetology. This is especially true since Vitamin C in the skin has another very important activity: it stimulates collagen synthesis by fibroblasts (Bernard 1998, Hata & Senoo 1989). However, Vitamin C is quite unstable, especially in the presence of water. This is why derivatives have been synthesized to stabilize it. But it is also known that many plants synthesize Vitamin C and often protect it by stabilizing it with proteins. This is why it is important to manufacture plant extracts using processes that preserve this protective environment.
[0007] The Kakadu plum (Terminalia ferdinandiana), also called Billygoat plum, Gubinge, or Murunga, is a flowering plant in the Combretaceae family, found in Australia, widespread in the woodlands from the Kimberley to eastern Arnherm Land, and particularly in the Kakadu region. Its fruit contains the highest amount of Vitamin C of any fruit, fifty to one hundred times more than that of an orange, and other free radical scavengers such as tocopherols and polyphenols (ellagic acid and chlorogenic acid). This high concentration is not unusual given that this region is particularly sunny and that the plants growing there are subjected to high doses of UV radiation, without being able to move to the shade. The ripe fruit is crushed into a puree which is then purified to remove solid parts and impurities.This purified puree is then freeze-dried using standard methods for this technique, which allows for cold extraction of water without heating and therefore without significant denaturation of Vitamin C and other antioxidants. The result is a dry extract containing 50 to 80% by weight of Vitamin C, which can be easily transported and stored. This extraction can be carried out using any other suitable method that preserves its qualities.
[0008] Kakadu plum extract was used soon after it became commercially available, and this use is specifically mentioned in patents EP 1981513 and EP 2944313. The intake of vitamin C through topical application of Kakadu plum extract (Terminalia ferdinandiana) is therefore beneficial to the skin in combating free radicals and skin aging.
[0009] To be active in the skin, vitamin C must be taken up and transported to where it is needed by a cell surface glycoprotein: Sodium-dependent Vitamin C Transporter Type 1 (SVCT-1). It turns out that Kakadu plum extract (Terminalia ferdinandiana) promotes the synthesis of this glycoprotein, which is very important for vitamin C metabolism.
[0010] Another manifestation of skin aging is the loss of elasticity, which is This is primarily due to a decrease in the dermis of key supporting molecules such as collagen, elastin, and glycosaminoglycans (GAGs). The extracellular matrix (ECM) refers to all the matrix components within the intracellular space. The extracellular matrix is mainly synthesized by fibroblasts in the dermis and acts as an interstitial medium. It allows contact between the dermis and the dermo-epidermal junction, and thus with the basal layer of the epidermis. The extracellular matrix is a reservoir of cytokines vital for cell survival and adaptability, such as growth factors.
[0011] The extracellular matrix is mainly composed of proteins (collagen, elastin), glycoproteins (fibronectin, laminins), and glycosaminoglycans and proteoglycans or GAGs (hyaluronic acid, chondroitin sulfate, aggregan, perlecan, among others). GAGs are linear polymers made up of repeating specific disaccharides. Hyaluronic acid (HA) is the most abundant GAG. It is a non-sulfated GAG (the only non-sulfated GAG), present as a sodium salt. It is formed from a repeating disaccharide of glucuronic acid and N-acetylglucosamine, linked together by alternating β-1,4 and β-1,3 glycosidic bonds.
[0012] Hyaluronic acid is synthesized by fibroblasts using a plasma membrane-bound enzyme (HA synthase). It is directly secreted into the intercellular space. Hyaluronic acid is an essential component of the extracellular matrix. Due to its remarkable physical properties, it plays a leading role in the structure and organization of the dermis, thus contributing to its firmness and elasticity. Furthermore, thanks to its water-retention capacity, hyaluronic acid plays a crucial role in regulating skin hydration.
[0013] It is observed that the HA content in the dermis and epidermis decreases with age. Mature skin experiences numerous alterations, such as loss of skin elasticity, the appearance of wrinkles, and dehydration, which are closely linked to the reduction in the amount of hyaluronic acid in the skin.
[0014] Collagen is present in many organs, in different types. Nearly 30 types are described in the scientific literature. Type I collagen, the most abundant in the human body, is mainly found in the skin, scar tissue, tendons, and certain parts of bones. Collagen is a protein present in the extracellular matrix and is synthesized by fibroblasts. Collagen is the supporting protein of the dermis. In aged skin, a decrease in its synthesis is observed compared to younger skin (Variani et al.). Furthermore, an increase in collagen degradation is observed in aged skin, particularly by reactive oxygen species and collagenases, which are called collagen-specific Matrix Metalloproteinases (MMPs). It is therefore It is essential to stimulate the synthesis of collagen I, which represents approximately 80% of dermal collagen.
[0015] The epidermis is composed of keratinocytes that differentiate from the basement membrane to the stratum corneum. The junction between the keratinocytes of the basal, spinous, and granular layers is ensured by desmosomes made up of proteins, the most important of which are ZO-1 and Occludin. This cohesion between keratinocytes regulates the variation in water content, which varies continuously from approximately 80% in the dermis and basement membrane to approximately 10% in the most superficial layers of the epidermis. These two proteins are therefore very important for the stability and moisture regulation of the epidermis. However, here again, a decrease in these proteins is observed with age, resulting in reduced cohesion of the epidermis, less undulation of the dermo-epidermal junction, and dry skin.
[0016] The supply of hyaluronic acid powder with a molecular weight between 10 and 60 kDa, preferably between 20 and 50 kDa, is beneficial for preventing and regenerating aging skin because it increases the synthesis of ZO-1 and Occludin proteins by keratinocytes in the epidermis and the synthesis of collagen I by fibroblasts in the dermis.
[0017] The hyaluronic acid used is manufactured by replicating a natural phenomenon. Certain lactic acid bacteria can produce hyaluronic acid, an essential component of their capsule. This extracellular production is a natural defense mechanism against stressful conditions. The chemical structure of the molecule produced by biotechnology is identical to that produced endogenously by human fibroblasts. In the first phase, cells of the selected (non-genetically modified) strain multiply on a substrate derived from wheat fractionation. In the second phase, the bacteria are placed under stressful conditions, which causes them to synthesize hyaluronic acid. The bacteria and proteins are then separated from the hyaluronic acid by sterile filtration.The polymer obtained then undergoes hydrolysis which yields a low molecular weight hyaluronic acid between 10 and 60 kDa, preferably between 20 and 50 kDa, appearing as a white powder, with a characteristic odor, containing more than 85% dry matter, and giving a clear solution after dissolution in water of 0.01% to 2%.
[0018] The thymus is an immune aging clock. It induces a cellular response thanks to T lymphocytes that mature in the thymus. This is a defense against pathogenic microorganisms and the development of cancer cells. The thymus undergoes involution starting around age 20; in particular, its active parts become fatty and inactive (Marc Vocansson, 2015). This results in a decrease in skin reactions to vaccines, an increase in infections, and Skin cancers and autoimmune diseases. The immune system ages and becomes less effective with age.
[0019] This decrease in the effectiveness of the immune system, or another persistent source of irritation such as chronic fatigue, certain medications, or poor diet, leads to low-grade but persistent inflammation. This chronic inflammation accelerates aging by unnecessarily mobilizing too many pro-inflammatory cytokines and metalloproteinases (MMPs), which degrade the supporting proteins of the dermis, resulting in excessive energy expenditure. This chronic inflammation alters the marking and therefore the expression of certain genes (as does chronic pain). This phenomenon is called inflammaging. To combat skin aging, it is therefore necessary to reduce its level of inflammation, even if it is low but persistent.
[0020] The Herculane spring is located in Romania, in the Cerna River valley, between the Mehedinti Mountains to the east and the Cerna Mountains to the west; it is a preserved natural area far from urban or industrial pollution. This area contains ancient forests and numerous other untapped springs. The water comes from a deep well (approximately 2,000 meters) and is bacteriologically pure. This spring is the oldest spa in Europe and was built by the Roman Emperor Traian in 102 AD and has been used ever since for its therapeutic properties. The water from this spring contains minerals at a level of 2,500 milligrams per liter, particularly calcium, magnesium, zinc, and small amounts of copper and manganese, with the anions being predominantly bicarbonate. This water is known for its free radical scavenging and anti-inflammatory properties, which have been confirmed by ex vivo and clinical tests on humans.
[0021] Furthermore, there is document GR1009780 which relates to cosmetic preparations having an anti-aging effect, such as serums and creams for the face and eyes, which include a mixture of basic hyaluronic acids, in combination with active plant extracts, such as pomegranate or grape or lupin or Kakadu plum, the vitamin C content of which is 100 times greater than that of an orange.
[0022] There is also document US2022088061 which discloses a pharmaceutical composition, preferably cosmetic or dermatological, comprising a polymer which may be hyaluronic acid and an active ingredient such as Kakadu plum extract to treat and / or prevent the aging of biological tissues in a synergistic manner.
[0023] TECHNICAL PROBLEM
[0024] There are therefore many cosmetic compositions in the prior art for treating skin aging. However, none of these compositions allows for a lasting effect on the signs of aging, and / or allows for to naturally restore / improve the skin's structure. Therefore, there is a real need to find new formulations capable of effectively treating skin aging and / or sustainably improving the skin's appearance, and / or improving the skin's structure.
[0025] DESCRIPTION OF THE INVENTION
[0026] The present invention aims precisely to meet these needs by proposing a cosmetic or pharmaceutical composition, comprising at least hyaluronic acid with a molecular weight between 10 and 60 kDa, preferably between 20 and 50 kDa, an extract of Kakadu plum (Terminalia femandiana) and thermal water from the Herculane spring.
[0027] The inventor has also surprisingly demonstrated that the effects obtained are visible and lasting. In particular, the inventor has demonstrated that the composition according to the invention advantageously allows for a visible and lasting reduction of the signs and markers of aging, for example, a reduction of wrinkles and fine lines, advantageously improving the appearance of the skin, which can advantageously appear younger, or more beautiful, for example, brighter, more supple, firmer, and also tighter skin.
[0028] More particularly, the present invention relates to cosmetic or pharmaceutical compositions intended to be applied to the skin and characterized in that, in order to prevent the main signs of skin aging, they preserve certain essential elements of the epidermis and dermis, they regenerate cohesive elements of the epidermis and support of the dermis and they have a soothing action thanks to the synergistic action of at least three ingredients: hyaluronic acid powder with a molecular weight between 10 and 60 kDa, preferably between 20 and 50 kDa, an extract of Kakadu plum (Terminalia ferdinandiana) in water-glycerin solution, dosed at 10 to 30% by weight of vitamin C, preferably dosed at 20% by weight of vitamin C and thermal water from the Herculane spring.
[0029] According to the present invention, Kakadu plum extract (Terminalia ferdinandiana) is prepared from a dry Kakadu plum extract dissolved in a mixture of water and glycerin, preferably a water / glycerin mixture with a 1 / 1 weight ratio.
[0030] According to the present invention, cosmetic or pharmaceutical compositions comprise at least hyaluronic acid powder with a molecular weight between 10 and 60 kDa, preferably between 20 and 50 kDa, an extract of Kakadu plum (Terminalia fermandiana) consisting of a solution of the dry extract in a mixture of half water and half glycerin by weight such that vitamin C is present at 20% by weight in this solution, and thermal water from the Herculane spring, the mineral components of which are bicarbonate (from 100 to 150 mg per litre, calcium (150 to 200 mg / l), magnesium (3.5 to 4.5 mg / l), iron (300 to 340 micrograms per litre), zinc (100 to 150pg / l), copper (20 to 30pg / l), manganese (30 to 55pg / l) characterized by the fact that the synergistic effect of these three active ingredients protects, through a synergistic anti-radical action, the essential elements of the epidermis and dermis such as essential fatty acids of cell walls, structural proteins such as collagen and elastin, the numerous enzymes necessary for the metabolism of cells and tissues, DNA which can continue its vital functions without being mutated and reduce chronic skin inflammation, which often increases all these deleterious effects.
[0031] According to the present invention, cosmetic or pharmaceutical compositions comprise at least hyaluronic acid with a molecular weight between 10 and 60 kDa, preferably between 20 and 50 kDa, an extract of Kakadu plum (Terminalia fer-mandiana) in water-glycerin solution dosed at 20% by weight of vitamin C and thermal water from the Herculane spring and characterized in that this anti-radical action described above is reinforced by the fact that the synergistic action of the three active ingredients stimulates the synthesis of the Sodium-dependent Vitamin C Transporter Type-1 (SVCT-1) receptor by the keratinocytes of the epidermis, which receptor facilitates the transport of vitamin C in the epidermis and the dermis, which vitamin C has a powerful anti-radical action and strongly stimulates the synthesis of collagen by the fibroblasts of the dermis.
[0032] According to the present invention, cosmetic or pharmaceutical compositions comprise at least hyaluronic acid with a molecular weight between 10 and 60 kDa, preferably between 20 and 50 kDa, an extract of Kakadu plum (Terminalia fer-mandiana) in water-glycerin solution dosed at 20% by weight of vitamin C and thermal water from the Herculane spring, characterized by the fact that the synergistic effect of these three active principles regenerates cohesive elements of the epidermis by stimulating the synthesis by the keratinocytes of the epidermal ZO-1 and Occludin proteins which constitute the tight junctions between keratinocytes and which are very important for the stability and hydration regulation of the epidermis.
[0033] According to the present invention, cosmetic or pharmaceutical compositions comprise at least hyaluronic acid with a molecular weight between 10 and 60 kDa, preferably between 20 and 50 kDa, and an extract of Kakadu plum (Terminalia fermandiana) in water-glycerin solution dosed at 10 to 30% by weight of vitamin C and thermal water from the Herculane spring, characterized by the fact that the synergistic effect of these three active ingredients regenerates elements of support, firmness, suppleness and elasticity of the skin by stimulating the synthesis of procollagen I by the fibroblasts of the dermis.
[0034] According to the present invention, cosmetic or pharmaceutical compositions contain at least hyaluronic acid with a molecular weight between 10 and 60 kDa, preferably between 20 and 50 kDa, an extract of Kakadu plum (Terminalia fer-mandiana) in water-glycerin solution dosed at 20% by weight of vitamin C and thermal water from the Herculane spring and characterized by the fact that the synergistic effect of these three active ingredients used in a cosmetic cream in clinical testing increases the radiance and firmness of the skin, reduces its roughness and the total length of crow's feet wrinkles and fine lines which are important signs of skin aging and reduces its inflammation which can aggravate these adverse effects.
[0035] More particularly, according to the present invention, cosmetic or pharmaceutical compositions include:
[0036] - hyaluronic acid with a molecular weight of 10 to 60 kDa, preferably 20 to 50 KDa,
[0037] - vitamin C, and
[0038] -an aqueous mineral solution comprising calcium, magnesium, iron, zinc, copper, manganese and bicarbonate.
[0039] More particularly, according to the present invention, the hyaluronic acid content represents 0.1 to 1%, preferably 0.3 to 0.5% by weight of the cosmetic or pharmaceutical composition.
[0040] More particularly, according to the present invention, vitamin C is a dry extract of Kakadu plum (Terminalia ferdinandiana) in water-glycerin solution.
[0041] More particularly, according to the present invention, the vitamin C content represents from 0.1 to 5%, preferably from 1 to 5% or from 2 to 5% by weight of the cosmetic or pharmaceutical composition.
[0042] More particularly, according to the present invention, the content of
[0043] - calcium in the composition is between 0.5 and 10 mg, preferably from 0.75 to 5 mg,
[0044] - magnesium in the composition is between 5 and 100 qg, preferably from 7.5 to 80 HQ,
[0045] - iron in the composition is comprised of 1 to 10 qg, preferably 1.5 to 6.8 qg,
[0046] - zinc in the composition is between 0.1 and 5 qg, preferably from 0.5 to 3 qg
[0047] - copper in the composition is between 0.05 and 1 qg, preferably 0.1 to 0.6 qg
[0048] - manganese in the composition is from 0.05 to 2 qg, preferably from 0.15 to Mqg,
[0049] - bicarbonate in the composition is between 0.1 and 5 mg, preferably from 0.5 to 3 mg.
[0050] More particularly, according to the present invention, the aqueous mineral solution is Herculane thermal water.
[0051] More particularly, according to the present invention, the thermal water content Herculane represents 5 to 20% by weight of the cosmetic or pharmaceutical composition.
[0052] More specifically, according to the present invention, the cosmetic or pharmaceutical composition comprises:
[0053] -from 0.1 to 1%, preferably from 0.3 to 0.5% by weight of hyaluronic acid with a molecular weight of 10 to 60 kDa, preferably from 20 to 50 kDa,
[0054] - 0.1 to 5% by weight of vitamin C supplied by a dry extract of Kakadu plum (Terminalia ferdinandiana) in water-glycerin solution, and
[0055] - from 5 to 20% by weight of an aqueous mineral solution, being thermal water Herculane including
[0056] -from 100 to 150 mg / l of bicarbonate,
[0057] - 150 to 200 mg / l of calcium,
[0058] -3.5 to 4.5 mg / l of magnesium,
[0059] -300 to 340 pg / l of iron,
[0060] - 100 to 150 pg / l of zinc
[0061] - 20 to 30 pg / l of copper, and
[0062] - from 30 to 55pg / l of manganese.
[0063] The cosmetic or pharmaceutical compositions of the present invention com They also contain active ingredients such as anti-dandruff agents, antimicrobials, nail care agents, oral hygiene agents, intimate hygiene agents, lipid restoration agents, tanning agents, vitamins, bacterial extracts, extracts of uni- or multi-cellular algae, anti-inflammatories, ceramides or pseudo-ceramides, α or β hydroxy acids, plant extracts, stem cell extracts, plankton extracts, extracts of revitalizing plants or plants living in extreme conditions, exopolysaccharides, polymer sugars, and extracts of recycled products.
[0064] The cosmetic or pharmaceutical compositions of the present invention may be presented in an appropriate form according to the rules of the art in use, in other forms such as liquids, pastes, creams, emulsions, lotions, oils, gels, masks, solids, powders, sprays, aerosols or any other form suitable for cosmetic or pharmaceutical uses, presented in suitable containers such as vials, bottles, jars, boxes, ampoules, capsules, pencils, stick holders or any other suitable container for cosmetic or pharmaceutical use.
[0065] The cosmetic or pharmaceutical compositions of the present invention may be in the form of oil / water or water / oil emulsions, twin-phase emulsions, microemulsions, PIT (Phase Inversion Temperature) emulsions, nanoemulsions, multiple water / oil / water or oil / water / oil emulsions, pseudoemulsions (dispersions of two immiscible phases stabilized by means of gel (lifiants), aqueous gels, oily gels, hydro-alcoholic gels, water-polyol gels, oily phases, suspensions, solid, liquid or pasty soaps, foaming solutions, or one of the preceding forms containing microcapsules, nanocapsules, liposomes.
[0066] The cosmetic or pharmaceutical compositions of the present invention may further include cosmetic or pharmaceutical adjuvants conventionally used as oil phase components, gelling agents, emulsifiers, electrolytes, humectants, sequestrants, emollients, moisturizing agents, film-forming agents, insoluble pigments, colorants, sunscreens, active ingredients or any other ingredient commonly used in cosmetic or pharmaceutical compositions.
[0067] a) Oily phase. The oily phase of the compositions of the present invention may contain, for example and without limitation: hydrocarbon oils such as paraffin or mineral oils such as isohexadecane and isododecane; natural oils such as sunflower oil, jojoba oil, hydrogenated or non-hydrogenated castor oil, avocado oil, hydrogenated or non-hydrogenated palm oil; unsaturated vegetable oils such as olive oil, evening primrose oil, linseed oil, avocado oil, borage oil, argan oil; triglycerides such as caprylic / capric triglyceride, caprylic / capric linoleic triglyceride, caprylic / capric succinic triglyceride; silicone oils such as cyclomethicones, dimethicones and dimethiconols; fatty alcohols such as stearic alcohol, cetyl alcohol and hexadecylic alcohol; fatty acids such as... stearic acid, palmitic acid, fatty acid esters such as dioctyl succinate, glyceryl dioleate,Myristyl myristate and isopropyl myristate, waxes such as beeswax, paraffin, camauba wax, ozokerite, lanolin and its derivatives (oil, alcohol, waxes), and mixtures thereof.
[0068] In the cosmetic or pharmaceutical compositions of the present invention, the oily phase can represent from 0.1 to 100% by weight, and preferably from 0.25 to 50%, by weight of the composition.
[0069] b) Gelling agents. The gelling agents that can be used in the cosmetic or pharmaceutical compositions of the present invention can be chosen from gelling agents known in the art, for example, polysaccharide gums such as modified cellulose derivatives, carrageenan derivatives, alginate derivatives and guar derivatives, polysaccharide gums obtained by bacterial fermentation such as xanthan gum, sclerotium gum and gellan gum, acrylic polymers such as carbomers, polyacrylates, polymethacrylates and their derivatives, quaternized polymers, PVP and PVP-derived polymers and mixtures thereof. In the cosmetic or pharmaceutical compositions of the present invention, the gelling agent or combination of gelling agents can represent from 0.1 to 30%, and preferably from 0.25 to 25%, by weight of the composition.
[0070] cl Emulsifiers. The emulsifiers that can be used in the cosmetic or pharmaceutical compositions of the present invention can be selected from emulsifiers known in the art, for example, but not limited to, sucrose esters such as sucrose cocoate and sucrose distearate, sorbitan esters such as sorbitan stearate and ethoxylated sorbitan esters such as polysorbate 80, glycerol esters, ethoxylated glycerol esters and polyglycerols such as glyceryl oleate or PEG-20 glyceryl stearate or polyglyceryl-10 stearate, ethoxylated fatty alcohols such as ceteth-12 or steareth-6, sesquioleates such as sorbitan sesquioleate, silicone oil-based emulsifiers such as silicone polyols, and ethoxylated plant sterols. or not, or a mixture of one or more of the emulsifiers mentioned above.The quantity of emulsifiers possibly present in cosmetic or pharmaceutical emulsions according to the present invention may vary from 0.1% to 40%, preferably from 0.5% to 25% by weight of said composition.
[0071] d) Other components. The following cosmetic or pharmaceutical compositions of the present invention may further comprise one or more other compounds which are known to those skilled in the art, for example: electrolytes for stabilizing water-in-oil emulsions such as sodium chloride or magnesium sulfate, preferably in an amount from about 0.2 to 4% by weight of the composition, humectants such as glycerin or propylene glycol or PEG or sorbitol, preferably in an amount from 0.1 to 40% by weight of the composition, sequestrants such as tetrasodium EDTA, preferably in an amount from about 0.001 to 2% by weight of the composition, emollients such as fatty acid ethers or fatty acid esters, preferably in an amount from about 0.5 to 30% by weight of the composition, moisturizing agents such as medium or high molecular weight hyaluronic acid, NaPCA, preferably in quantities ranging from about 0.01 to 20% by weight of the composition, film-forming agents to facilitate spreading on the skin surface, such as hydrolysates of oat, wheat, collagen and almond proteins, preferably in quantities ranging from about 0.1 to 5% by weight of the composition, insoluble pigments such as titanium dioxide, rutile titanium dioxide, anatase titanium dioxide, pyrogenated titanium dioxide, micronized titanium dioxide, titanium dioxide surface-treated with silicones or amino acids, or lecithin, or metallic stearates, iron oxides, iron oxides surface-treated with silicones, or amino acids, or lecithin or metallic stearates, zinc oxide, micronized zinc oxide, titanium dioxide-coated mica, preferably in an amount of about 0.5 to 10% by weight of the composition and mixtures thereof, water-soluble or fat-soluble colorants, fixed or. not on carriers (lacquers), such as CI 19140, CI 42090, CI 40800, for skin or hair, sunscreens such as Octyl Methoxycinnamate, Oxybenzone, Octocrylene, Benzylidene Camphor, sulfonic acid, Octyl Salicylate, Octyl Triazone, 3-Benzylydene Camphor, Butyl Methoxydibenzoyl Methane in quantities permitted by the regulations governing the manufacture of cosmetic products, which vary from country to country, active ingredients intended to enhance the activity of cosmetic or pharmaceutical products in other areas of skin care and related products, such as, for example, but not limited to, anti-dandruff agents, antimicrobial agents, nail care agents, oral hygiene agents, intimate hygiene agents, lipid-restoring agents, tanning agents, vitamins such as Vitamins A, C, E, bacterial extracts, extracts of unicellular or multicellular algae,Anti-inflammatory agents such as enoxolone or ursolic acid, ceramides (III,II) or pseudo-ceramides, peptides such as pyroGlu-Glu-Asp-Ser-GlyOH or Gly-His-Lys or Arg-Gly-Asp-Ser, alpha or beta hydroxy acids such as lactic acid, glycolic acid, salicylic acid, plant extracts selected for their biological activity such as extracts of licorice, Centella asiatica, Boswellia serrata, grapevine shoot, soy, saw palmetto, Epilobium roseum, Angelica sinensis, Dioscorea villosa, apple seeds, Lepidum peruvianum, Actaea racemosa, Salix alba, Canlendula officinalis, ginseng, Sophora japonica, Eucalyptus macrorrhyncha, Ginkgo biloba, passionflower incarnata, Silibum marianum, Helichrysum stoechas, Green tea, Achillea millefolium, extracts of stem cells from various plants, extracts of plankton, revitalizing plants or plants living in extreme conditions such as Myrothamus flabellifolia, Rhodiola serrulata,Chaparal, Schinus molle, Acer rubum, Dicea mariana, exo-polysaccharides produced by plankton, found for example in the Aber Wrach or the Iroise Sea (Brittany region, France), polymeric sugars such as β-poly-β-1-3 glucopyranose extracted from yeast membranes, extracts of recycled products such as vine shoots, orange or mandarin peels after juice extraction.
[0072] The cosmetic or pharmaceutical compositions of the present invention may further contain preservatives, antiperspirants, antistatics, bleaching agents, buffers, foaming agents, chelating agents, depilatory agents, detangling agents, foaming agents, masking agents, opacifying agents, pearlescent agents, plasticizers, propellants, refreshing agents, solvents or any other agent suitable for cosmetic or pharmaceutical use.
[0073] All these active or complementary agents can be incorporated into the cosmetic or pharmaceutical compositions of the present invention, in proportions from 0.001 to 50% and their list is in no way limiting.
[0074] In all that follows or precedes, percentages are given by weight except unless otherwise stated.
[0075] EXPERIMENTAL SECTION Example 1
[0076] Anti-radical effect test.
[0077] Diphenylpicrylhydrazyl (DPPH) is a free radical that is used to measure the anti-radical activity of a substance by its ability to scavenge DPPH free radicals. A triple test was performed with Kakadu plum extract in a 20% hydro-glycolic solution of vitamin C, tested at 1% in distilled water (designated K 1 in Table 1 below) after 30 minutes and 24 hours, as well as hyaluronic acid powder with a molecular weight of 20 to 50 kDa, tested at 0.5% in distilled water (designated HA bpm 0.5), a mixture of the two previous solutions and Herculane thermal water diluted to 5% in distilled water, and finally, a mixture of Kakadu plum extract in a 20% water-glycerin solution of vitamin C, hyaluronic acid powder between 10 and 60 kDa, preferably between 20 and 50 kDa at 0.5%, and Herculane thermal water at 5% in distilled water. (called Mixture).The results are expressed as a percentage increase in anti-radical activity compared to the control value (distilled water without added active ingredient).
[0078] [Tables] Active ingredient tested. Antioxidant effect at 30 minutes. Antioxidant effect at 24 hours. K1 +54% + / - 2% +69% + / - 2. HA bpm 0.5 +22 = -0.5% +29% + / - 1%. Kl + HA bpm 0.5 102 + / - 2% 135 + / - 2%. Herculane Thermal Water 5% +5% + / - 0.5% +8% + / - 0.5%. Mixture 122% + / - 2% +152% + / - 2%
[0079] We see that the mixture of the 2 active ingredients, Kakadu plum extract and bpm hyaluronic acid, gives a synergistic result superior to the sum of the results of the active ingredients alone, and the addition of Herculane thermal water reinforces this anti-radical synergistic effect. Example 2
[0080] Stimulation test of the synthesis of the SVCT-1 receptor (Sodium-dependent Vitamin C Transporter Tvpe-1).
[0081] The test is performed in triplicate on cultures of human keratinocytes. The concentrations of the active ingredients in distilled water are lower than those used in a complete cosmetic product because they are in direct and immediate contact with epidermal cells, whereas, in a complete cosmetic product, contact occurs after dilution in the stratum corneum and then the other layers. of the epidermis, resulting in significant dilution before contact with living cells. To determine the optimal concentrations for use in such an in vitro test, the maximum concentration of each active ingredient that does not damage the cells used in the test is first determined. 10 mM iron chloride (FeCl3) was used as a positive control. SVCT-1 synthesis was measured by ELISA after 24 hours. The results are expressed as a percentage increase in SVCT-1 receptor synthesis compared to the control condition (without added active ingredient). The active ingredients tested are Kakadu plum extract in a 20% water-glycerin solution of vitamin C and tested at 0.1% in distilled water (named K 0.1), hyaluronic acid powder with a molecular weight of 20 to 50 KDA tested at 0.05% in distilled water (named HA bpm 0.05), the mixture of the two previous ones and Herculane thermal water at 2% in distilled water and the mixture of Kakadu plum extract in a 20% water-glycerin solution of 0.1% vitamin C, 0.05% hyaluronic acid bpm and Herculane thermal water at 8% (called Mixture) in distilled water. The results are summarized in Table 2: .
[0082] [Tables2] Active ingredient tested: SVCT-1 synthesis. Result at 24h: Distilled water (negative control) 0% FeCl3 (positive control) +225% + / -2% K 0.2 +106% + / -1.3% HA bpm 0.1 +15% + / -0.8% K 0.2 + HA bpm 0.1 142 + / -1.4% Herculane thermal water 8% +9% + / -0.1% Mixture +158% + / -1.4%
[0083] In this test too we see that the mixture of the 2 active ingredients, Kakadu plum extract and bpm hyaluronic acid gives a synergistic result superior to the sum of the results of the active ingredients alone and the addition of Herculane thermal water reinforces this anti-radical synergistic effect. Example 3
[0084] Test for stimulating the synthesis of ZO-1 proteins by keratinocytes and Occludin is a constituent of tight junctions between keratinocytes in the epidermis. These two proteins are crucial for epidermal stability and moisture regulation. The test was performed on normal human keratinocytes obtained from plastic surgery. They were seeded in 12-well plates with appropriate culture medium and incubated for 24 hours. After incubation, the culture medium was refreshed with fresh medium containing or not containing the products to be tested. The cells were then incubated for 72 hours at 37°C under a 5% carbon dioxide atmosphere. The experiment was performed in triplicate for each condition.
[0085] Membrane proteins are extracted with an appropriate buffer and then loaded at 3.6pg / well and then separated on a suitable electrophoresis gel.
[0086] After migration, the proteins are transferred to a nitrocellulose membrane, which is saturated with a suitable buffer for non-specific sites. After washing, the specific antigenic sites are labeled with an anti-ZO-1 or anti-Occludin monoclonal antibody. These are detected, after one hour of incubation at room temperature and washing, using a second antibody conjugated to peroxidase. Peroxidase activity is detected by chemiluminescence. Here again, the maximum concentrations are predetermined for each active ingredient to avoid interference with the viability of living cells. The active ingredients tested are Kakadu plum extract in water-glycerin solution with 20% vitamin C tested at 0.2% in distilled water (named K 0.2), hyaluronic acid powder with a molecular weight of 20 to 50 kDa tested at 0.1% in distilled water (named HA bpm 0.1) Herculane thermal water tested at 5% in distilled water and the mixture of Kakadu plum extract in water-glycerin solution at 20% vitamin C at 0.2%, hyaluronic acid powder with a molecular weight of 20 to 50 kDa at 0.1% and Herculane thermal water at 5% in distilled water (called the Mixture). The results expressed in quantities of synthesized proteins are summarized in Table 3: .
[0087] [Tables3] Active ingredient tested: ZO-1 Occludine Control 100 100 K 0.2 129 139 Herculane Thermal Water 10% 12 25 HA bpm 0.1 110 105 Mixture 296 303
[0088] Here too, we see that the mixture of the 3 active ingredients gives superior biological activity to the sum of the results of the active ingredients alone, and that, therefore, the mixture of these active ingredients is synergistic to stimulate the synthesis of ZO-1 and Occludine proteins by normal human keratinocytes, proteins important for the regulation of hydration of the upper layers of the epidermis and useful for fighting against skin aging. Example 4
[0089] Pro-Collagen I. Stimulation Test
[0090] The test was performed on normal human fibroblasts obtained from plastic surgery. They are seeded in 12-well plates in appropriate culture medium and incubated for 48 h in the presence of the products to be tested.
[0091] Keratinocytes synthesize pro-Collagen I, which, in the skin, will be used to produce Collagen I. In the test, the supernatants containing pro-Collagen are collected, stored at -20°C and then tested with a specific kit.
[0092] Vitamin C is also tested as a positive control for pro-Collagen I synthesis at a dose of 5 mg / ml. Kakadu plum extract in a 20% water-glycerin solution of vitamin C, tested at a dose of 5 mg / ml (referred to as Kakdu Plum Extract 5 mg / ml), hyaluronic acid powder with a molecular weight of 20 to 50 kDa, tested at a dose of 5 mg / ml (referred to as HA bpm 5 mg / ml), Herculane thermal water diluted to 20% in distilled water, and a mixture of these last three active ingredients at the same doses are also tested. The results are shown in Table 4:
[0093] [Tables4] Active ingredient tested: Relative stimulation of pro-collagen synthesis I Vitamin C positive control reference 100 Distilled water negative control 0 Kakadu plum extract 5 mg / ml 90 HA bpm 5 mg / ml 121 Kakadu plum extract 5 mg / ml + HA bpm 5 mg / ml 255 Herculane thermal water 20% 10 Mixture 272
[0094] It can be seen that Kakadu plum extract, which contains 20% by weight of vitamin C, stimulates the synthesis of pro-collagen I almost as much as pure vitamin C. The action The concentration of low molecular weight hyaluronic acid is superior, the mixture of these two active ingredients is superior to the active ingredients alone, and the mixture of all three active ingredients is even superior, which clearly demonstrates once again the synergistic effect of this mixture. Example 5
[0095] Test on the release of histamine on human skin expiants.
[0096] Neurogenic inflammation leads to skin irritation due to the local release of neuropeptides, including substance P. This neurotransmitter is indeed one of the factors responsible for the inflammatory response. Substance P acts directly on the vascular wall, causing edema, vasodilation, and mast cell degranulation with the release of histamine (Eur. J. Dermatol 1995;5:349-357). The potential calming effect of an active ingredient on histamine release can be tested in a human skin explant model stimulated or not with substance P. The test was performed with 8 mm diameter healthy human skin explants obtained from surgical abdominal reconstructions of two donors, one aged 32 years and the other 63 years. They are placed in 24-well plates and stabilized in an oven at 37°C, 5% CO2 for 4 hours in a suitable survival medium.
[0097] After application of substance P (at IpM in calcium-free phosphate saline buffer PBS) for 1 hour, the supernatants are collected and histamine is measured with an ELISA kit.
[0098] The expellents are then treated twice with the different active ingredients at a dose of 100 µL of the solutions in distilled water: Kakadu plum extract in a 20% hydroglycolic solution, 3% vitamin C in distilled water, hyaluronic acid with a molecular weight between 20 and 50 kDa at 1% in distilled water, Herculane thermal water diluted to 20% in distilled water, and a mixture of these three active ingredients at the same doses in distilled water. The results are expressed as the quantity of histamine released and are summarized in the following table:
[0099] [Tables5] Active ingredient tested Donor 32 years old Donor 63 years old Histamine released Histamine released Buffer+ + substance P 10 12.1 Distilled water negative control 0 Kakadu plum extract 3% 6.0 8.7 HA bpm 1% 7.1 5.5 Kakadu plum extract 3% + HA bpm 1% 4.8 4.9 Herculane thermal water 20% 4.4 25 Mixture of 3 1.5 1.8
[0100] We see that the mixture of the 2 active ingredients Kakadu plum extract and bpm hyaluronic acid gives a better result than the sum of the results of each of the 2 active ingredients taken separately and that the addition of Herculane thermal water further reinforces this synergistic effect by reducing the amount of histamine released by substance P, hence a powerful anti-inflammatory effect.
[0101] Example 6.
[0102] Cosmetic cream prepared with a mixture of Kakadu plum extract and low molecular weight hyaluronic acid, and including 20% by weight of Herculane thermal water, for the facial care of mature skin: The following oily phase is prepared:
[0103] Arachidyl Alcohol & Behenyl Alcohol & Arachidyl Glucoside 4g
[0104] Jojoba Oil 4g
[0105] Caprylic / Capric Triglycerides 4g
[0106] Jojoba Esters 1g
[0107] Hydrogenated Polyisobutene 4g
[0108] Isocetyl Stearate 4g
[0109] Cetyl ricinoleate 4g
[0110] Shea Butter 1g [YES] Dipentaerythrityl Hexacaprylate / Hexacaprate 3g
[0112] This mixture is heated to 70°C and thoroughly homogenized.
[0113] Furthermore, the following aqueous phase is prepared:
[0114] Purified Water QS100
[0115] Herculane thermal water 20g
[0116] Tetrasodium EDTA 0.05g
[0117] Glyceryl Polymethacrylate / Propylene Glycol 5g
[0118] Cellulo se 2g
[0119] Silica beads coated with metal oxides 1g
[0120] Sodium Acryloyldimethyltaurate Copolymer & Isohexadecane & Polysorbate 80 1.25g
[0121] All the ingredients of the aqueous phase are dissolved in water and the mixture is heated to 70°C. The homogeneous oil phase, also heated to 70°C, is slowly poured onto the aqueous phase, which has been heated to the same temperature, while stirring vigorously. Stirring is maintained for 10 minutes after the oil phase has been added. An oil-in-water emulsion is formed.
[0122] Next, the emulsion is cooled under moderate stirring.
[0123] When the temperature reaches 40°C, the following are added successively under moderate stirring
[0124] Hyaluronic acid powder, molecular weight 20 to 50 kDa, 0.3 g
[0125] Kakadu plum extract with 20% vitamin C 0.5g equivalent to 0.2g of vitamin C
[0126] Preservatives 0.15g
[0127] Perfume 0.3g
[0128] After homogenization, the emulsion is cooled to 30°C under slow stirring.
[0129] This gives a white emulsion of pleasant consistency, suitable for mature skin which tends to become dry, rough, with less firmness and with the appearance of wrinkles and fine lines.
[0130] Example 7. Anti-aging oil / water emulsion
[0131] The fatty phase consists of:
[0132] Caprylic / Capric Triglycerides 8g
[0133] Isodecyl Neopentanoate 5g
[0134] Hydrogenated Polyisobutene 5g
[0135] Jojoba Oil 5g
[0136] Cetyl Alcohol 1g
[0137] Stearic Acid 1g
[0138] Beeswax 1 g
[0139] Glycerol Stearate 0.5g
[0140] This fatty phase is heated to 70°C and thoroughly homogenized.
[0141] Furthermore, the following aqueous phase is prepared:
[0142] Purified water QS 100g
[0143] Herculane thermal water 5g
[0144] Tetrasodium EDTA 0.05g
[0145] Glycerin 3g
[0146] Sorbitol 2g
[0147] Carbomer 0.25g
[0148] Xanthan Gum 0.2g
[0149] Biosaccharide Gum-1 0.5g
[0150] Polyethylene Glycol 400 2g
[0151] Preservatives 0.5g
[0152] 10% sodium hydroxide 0.5g
[0153] All the ingredients of the aqueous phase are dissolved in water and the mixture is heated to 70°C.
[0154] The homogeneous oil phase, heated to 70°C, is slowly poured onto the aqueous phase, which has been brought to the same temperature, while stirring vigorously. Stirring is maintained for 10 minutes after the oil phase has been added. An oil-in-water emulsion is formed.
[0155] Vigorous agitation is then continued for at least 10 minutes.
[0156] Next, the emulsion is cooled under moderate stirring.
[0157] When the temperature reaches 40°C, the following are added successively under moderate stirring
[0158] Hyaluronic acid powder, molecular weight 20 to 50 kDa, 0.1 g
[0159] Kakadu plum extract with 20% vitamin C 0.5g equivalent to 0.2g of vitamin C
[0160] Perfume 0.35g
[0161] After homogenization, the emulsion is cooled to 30°C under slow stirring.
[0162] A white, smooth cream with a very fresh feel is obtained to combat the effects of aging such as dryness of the skin, loss of radiance and firmness of the skin, the appearance of a certain roughness and wrinkles and fine lines.
[0163] Example 9. Lamellar phase oil / water emulsion for face and body
[0164] The fatty phase consists of:
[0165] Cetearyl Alcohol & Cetearyl Glucoside 6g
[0166] Octyl Stearate 2g
[0167] Beeswax 1.5g
[0168] Propylene Glycol Dicaprylate / Dicaprate 2.5g
[0169] Jojoba Oil 4g
[0170] Shea Butter 4g
[0171] This oily phase is heated to 80°C and thoroughly homogenized.
[0172] Furthermore, the following aqueous phase is prepared:
[0173] Purified water QS 100g
[0174] Herculane thermal water 20g
[0175] Tetrasodium EDTA 0.05g
[0176] Glyceryl Polymethacrylate & Propylene Glycol 10g
[0177] Preservatives 0.5g
[0178] All the ingredients of the aqueous phase are dissolved in water and the mixture is heated to 80°C.
[0179] The oil phase, homogeneous and heated to 80°C, is slowly poured onto the aqueous phase, which has been brought to the same temperature, while stirring vigorously. Stirring is maintained for 10 minutes after the oil phase has been added. An oil-in-water emulsion is formed.
[0180] Next, the emulsion is cooled under moderate stirring.
[0181] When the temperature reaches 40°C, the following are added successively under moderate stirring
[0182] Hyaluronic acid powder, molecular weight 20 to 50 kDa, 1 g
[0183] Kakadu plum extract with 20% vitamin C 2.0g equivalent to 0.4g of vitamin C
[0184] Perfume 0.35%
[0185] After homogenization, the emulsion is cooled to 30°C under slow stirring.
[0186] A very smooth, white cream with lamellar phases is obtained, which can facilitate the penetration of active ingredients and provide prolonged hydration. It is perfectly suited for facial and body care, particularly for increasing radiance and skin luminosity, reducing roughness, diminishing the overall length of crow's feet and fine lines, and restoring skin firmness.
[0187] Example 10: treatment foundation.
[0188] The next fatty phase is prepared:
[0189] Cetyl Alcohol 1 g
[0190] Glyceryl Stearate 2g
[0191] Stearic Acid 1g
[0192] Tocopherol acetate 0.5g
[0193] Jojoba Oil 3g
[0194] Perfluoro Polymethyl Isopropyl Ether 0.5g
[0195] Cetearyl Octanoate 6g
[0196] Diisostearyl Malate 8g
[0197] This oily phase is heated to 80°C and thoroughly homogenized.
[0198] Furthermore, the following aqueous phase is prepared:
[0199] Purified water QS 100g
[0200] Herculane thermal water 15g
[0201] Tetrasodium EDTA 0.05g
[0202] Xanthan gum 0.3g
[0203] Preservatives 0.6g
[0204] All the ingredients of the aqueous phase are dissolved in water and the whole is The oil phase, heated to 80°C, is slowly poured onto the aqueous phase, which has been heated to the same temperature, while stirring vigorously. Stirring is maintained for 10 minutes after the oil phase has been added. An oil-in-water emulsion is formed.
[0205] Next, the pigments and talc are added and vigorously mixed while hot:
[0206] Titanium dioxide 6.3g
[0207] Mixture of Yellow Iron Oxide and Talc 4.1g
[0208] Mixture of Red Iron Oxide and Talc 0.2g
[0209] Mixture of Brown Iron Oxide and Talc 1.5g
[0210] Talc 5g
[0211] When the coloured emulsion is perfectly homogeneous, cooling begins under moderate stirring.
[0212] After thorough homogenization and when the temperature reaches 40°C, the following is added under moderate stirring:
[0213] Hyaluronic acid powder, molecular weight 10 to 60 kDa, 1.0 g
[0214] Kakadu plum extract with 20% vitamin C 5g, equivalent to 1g of vitamin C
[0215] Perfume 0.35g
[0216] After homogenization, the emulsion is cooled to 30°C under slow stirring.
[0217] A foundation is obtained for treatment makeup for wrinkled and dull skin. Example 11
[0218] Clinical validation test of the synergistic action on the skin of the mixture of Kakadu plum extract with 20% vitamin C at a dose of 2% i.e. 0.4g of vitamin C, hyaluronic acid with a molecular weight between 20 and 50 kDa at a dose of 11% and Herculane thermal water at a dose of 20% introduced into the cosmetic cream of example 9.
[0219] The test is conducted on 88 female volunteers with phototypes I to IV, aged between 35 and 65 years (mean age 48 years), who have dry skin, wrinkles and fine lines around the eyes (crow's feet), somewhat rough skin, and a rather dull complexion. The participants do not have psoriasis, eczema, erythema, edema, scars, or any other lesions on their face. They have not started, changed, or stopped hormone replacement therapy during the three months prior to the start of the test or during the test period. They have not applied any anti-wrinkle products (e.g., based on alpha-hydroxy acids, fruit acids, or retinol) for at least two weeks prior to the start of the test. Participants agree not to use any other facial cosmetic products other than the product being tested during the test period, except for makeup removers, toners or makeup without claims of skincare benefits.
[0220] Individuals agree not to use any medication during the test period. containing aspirin, steroidal or non-steroidal anti-inflammatory drugs, DHEA (only limited use of paracetamol is permitted).
[0221] No cosmetic product (including the product to be tested) may be used on the areas studied on the measurement days.
[0222] The volunteers are divided into 4 groups of 22 volunteers each, homogeneous groups for all the aforementioned criteria. The cream is prepared according to the formula of Example 9 and 10, with other creams modified as follows: a placebo cream or Kakadu plum extract with 28% vitamin C and hyaluronic acid powder with a molecular weight of 20 to 50 kDa and Herculane thermal water are replaced by purified water; a cream containing only Kakadu plum extract with 28% vitamin C at a concentration of 2%; a cream containing only hyaluronic acid powder with a molecular weight of 20 to 50 kDa at a concentration of 1%; and finally, a cream containing 22% Herculane thermal water. All 5 of these creams are applied to one side of the face twice a day for 30 days.
[0223] For skin radiance, radiance is measured by spectrometry / colorimetry at J0 and J30.
[0224] Roughness is assessed for each volunteer by a Dermatologist according to the scale described in Table 6:
[0225] [Tableauxô] Skin Condition Score: 0 Smooth skin 1 Very slightly rough skin 2 Slightly rough skin 3 Moderately rough skin 4 Very rough skin
[0226] The quantities to be used are those that people usually use for this type of product on their face.
[0227] This is an open-label study: both the investigators and the participants are aware of the study's objective. It is a non-comparative study. Each participant serves as their own reference on day 0. The method used involves silicone replicas of the crow's feet. The selection of the crow's feet to be measured is randomized using specific software.
[0228] Individuals must arrive for measurements without any makeup or cosmetic products on their face. After 15 minutes of acclimatization to 21°C ± 1°C, humidity 45% ± 5%, individuals are placed in a semi-reclined position in a suitable chair. The positioning of the subjects is the even from one measurement to the next thanks to recessed markings in the file.
[0229] Crow's feet impressions are made using 8g of silicone resin (Silflo, Flexico Developments Ltd, Great Britain) mixed with 8 drops of catalyst using a spatula. An impression of the entire crow's foot is taken. This includes 5 cm from the corner of the eye to the hairline, at least 3 cm towards the eyebrow and forehead, and at least 3 cm towards the cheek. During the impression-taking, the person's eye remains open, and their head is upright. After 10 minutes, the impression is removed from the skin. The person's number, the side examined, and the date of the measurement (D-O and D-30) are noted on the back of the impression. The impressions are analyzed using the shadow method, which allows for the measurement of the total wrinkle length and the total wrinkle area in the studied region. We can therefore measure the evolution of these parameters between the start of the test (JO) and the end of the test (J30).Skin firmness is measured using a Cutometer®, which is designed to measure the biomechanical properties of the upper layers of the epidermis by applying negative pressure (suction) that deforms the skin. The measurement principle is based on the suction method. Negative pressure is created within the device, and the skin is drawn into the measuring cup of the probe. After a set time, the skin is released inside the probe. The depth of penetration is determined by a non-contact optical measurement system. This optical measurement system consists of a light source and a light receiver. The intensity of the light varies according to the depth of skin penetration. The skin's resistance to negative pressure (firmness) and its ability to return to its original position (elasticity) are displayed as curves (depth of penetration in mm / unit of time) in real time during the measurement.This measurement principle provides information on the elasticity and mechanical properties of the skin surface.
[0230] The results of all these tests are summarized in Table 7.
[0231] [Tables?] Results at Day 30 compared to Day 1: Radiance, skin radiance, skin roughness, total length of crow's feet and wrinkles, skin firmness measured by Cutometer®. Group 1: Placebo-treated side -0.4% -0.6% -2% +2%. Group 1: Side treated with Kakadu plum extract 2% +17% -11% -12% +15%. Group 2: Placebo-treated side -0.3% -0.5% -1.8% +2.5%. Group 2: Side treated with HA bpm 1% +12% -12% -13% +17%. Group 3: Placebo-treated side -0.4% -0.8% -1.5% +1.2%. Group 3: Side treated with Herculane thermal water 22% +8% -6% -10% +8%. Group 4: Placebo-treated side -0.3% -0.4% -2.1% +1.6%. Group 4: Side treated with plum extract mixture Kakadu and hyaluronic acid +34% -26% -29% +36% Group 5 Placebo-treated side -0.3% -0.5% -1.8% +1.5% Group 5 Mixture-treated side +45% -35% -43% +49% complete
[0232] As with the in-vitro and ex-vivo results previously described, the clinical test on humans with measurements carried out on several significant criteria of the skin condition shows that the action of a Kakadu plum extract with 20% vitamin C at a dose of 2% or hyaluronic acid powder with a molecular weight of 20 to 50KDa at a dose of 1% or Herculane thermal water at a dose of 22% has beneficial effects on the skin of volunteers after 30 days of application twice a day (radiance, skin luminosity, skin roughness, total length of crow's feet and fine lines, skin firmness) and especially that the mixture of the first two active ingredients gives surprisingly superior results to the sum of the results of creams containing only one of the two active ingredients, in comparison of each volunteer to the half of the face which received the placebo cream (without any of the three active ingredients).And the addition of Herculane thermal water further reinforces all these synergistic results in clinical testing on human skin.
Claims
Demands
1. A cosmetic or pharmaceutical composition, characterized in that it comprises: - hyaluronic acid with a molecular weight of 10 to 60 kDa, preferably 20 to 50 kDa, - vitamin C, being a dry extract of Kakadu plum (Terminalia ferdinandiana), in a water-glycerin solution, and - an aqueous mineral solution comprising calcium, magnesium, iron, zinc, copper, manganese, and bicarbonate, wherein the content of: - calcium in the composition is 0.5 to 10 mg, preferably 0.75 to 5 mg, - magnesium in the composition is 5 to 100 qg, preferably 7.5 to 80 qg, - iron in the composition is 1 to 10 qg, preferably 1.5 to 6.8 qg, - zinc in the composition is 0.1 to 5 qg, preferably 0.5 to 3 qg, - copper in The composition is between 0.05 and 1 qg, preferably 0.1 to 0.6 qg - manganese in the composition is between 0.05 and 2 qg, preferably 0.15 to 1.1 qg,- bicarbonate in the composition is between 0.1 and 5 mg, preferably between 0.5 and 3 mg.
2. Composition according to claim 1 characterized in that the hyaluronic acid content represents from 0.1 to 1%, preferably from 0.3 to 0.5% by weight of the composition.
3. Composition according to claim 1 characterized in that the vitamin C content represents from 0.1 to 5% by weight of the composition.
4. Composition according to claim 1 characterized in that the aqueous mineral solution is Herculane thermal water.
5. Composition according to claim 6 characterized in that the content of Herculane thermal water represents from 5 to 20% by weight of the composition.
6. Composition according to claim 1 characterized in that it comprises: -from 0.1 to 1%, preferably from 0.3 to 0.5% by weight of hyaluronic acid with a molecular weight of 10 to 60 kDa, preferably from 20 to 50 KDa, - 0.1 to 5% by weight of vitamin C supplied by a dry extract of Kakadu plum (Terminalia ferdinandiana) in water-glycerin solution, and - 5 to 20% by weight of an aqueous mineral solution being Herculane thermal water comprising - 100 to 150 mg / l of bicarbonate, - 150 to 200 mg / l of calcium, - 3.5 to 4.5 mg / l of magnesium, - 300 to 340 pg / l of iron, - 100 to 150 pg / l of zinc - 20 to 30 pg / l of copper, and - 30 to 55 pg / l of manganese.
7. Composition according to any one of the preceding claims, characterized in that it further comprises active ingredients such as anti-dandruff agents, antimicrobials, nail care agents, oral hygiene agents, intimate hygiene agents, lipid restoration agents, tanning agents, vitamins, bacterial extracts, extracts of uni- or multi-cellular algae, anti-inflammatories, ceramides or pseudo-ceramides, α or β hydroxy acids, plant extracts, stem cell extracts, plankton extracts, extracts of revitalizing plants or plants living in extreme conditions, exopolysaccharides, polymer sugars, extracts of recycled products.
8. Composition according to any one of the preceding claims, characterized in that it further comprises oil phase components, gelling agents, emulsifiers, electrolytes, humectants, sequestrants, emollients, moisturizing agents, film-forming agents, insoluble pigments, colorants, sunscreens, preservatives, antiperspirants, antistatics, bleaching agents, buffers, foaming agents, chelating agents, depilatory agents, detangling agents, foaming agents, masking agents, opacifying agents, pearlescent agents, plasticizers, propellants, refreshing agents, solvents or any other agent suitable for cosmetic or pharmaceutical use, active ingredients and / or any other ingredient or mixture of ingredients usually used in cosmetic or pharmaceutical compositions.
9. A composition according to any one of the preceding claims, characterized in that it is in the form of liquids, pastes, creams, emulsions, lotions, oils, gels, masks, solids, Powders, sprays, aerosols, or other suitable forms, presented in containers such as vials, bottles, jars, boxes, ampoules, capsules, pencils, stick holders, or other suitable containers, in particular oil-in-water or water-in-oil emulsions, twin-phase emulsions, microemulsions, PIT emulsions, nanoemulsions, multiple water-in-oil-in-water or oil-in-water-in-oil emulsions, pseudoemulsions (dispersions of two immiscible phases stabilized by means of gelling agents), aqueous gels, fatty gels, hydroalcoholic gels, water-polyol gels, fatty phases, suspensions, solid, liquid, or paste soaps, foaming solutions, or any of the preceding forms containing microcapsules, nanocapsules, or liposomes
10. A cosmetic treatment method, advantageously for combating oxidative stress, and in particular cellular aging of the skin, consisting of applying to the skin the cosmetic composition according to any one of claims 1 to 10.
11. Use of a composition according to any one of the preceding claims for: - a synergistic anti-radical action preserving the essential elements of the epidermis and dermis, - a synergistic action of stimulating the synthesis of the SVCT-1 (Sodium-dependent Vitamin C Transporter Type-1) receptor on keratinocyte cultures measured by ELISA, this stimulation reinforcing the anti-radical action of the combination of the three active ingredients, - a synergistic action of stimulating the synthesis by keratinocytes of the ZO-1 and Occludin proteins constituting the tight junctions between keratinocytes in the epidermis, and strengthening the cohesion of the epidermis and ensuring its hydration regulation, - a synergistic action of stimulating the synthesis of procollagen I by dermal fibroblasts and thus regenerating supporting elements of the dermis, promoting increased firmness, suppleness and elasticity of the skin,and - a synergistic action to improve skin radiance and luminosity, skin roughness, and skin firmness, and a synergistic action to reduce the total length of crow's feet wrinkles and fine lines in clinical trials on human volunteers.