FR3147714A1 - Cosmetic or pharmaceutical compositions comprising at least hyaluronic acid, a Kakadu plum extract and thermal water from the Herculane spring. - Google Patents

Abstract

The present invention relates to the preparation of cosmetic or pharmaceutical compositions having an anti-aging effect. The present invention describes more particularly a cosmetic or pharmaceutical composition comprising at least hyaluronic acid of molecular weight between 20 and 60 kDa, an extract of Kakadu plum (Terminalia fernandiana) and thermal water from the Herculane spring (No figure)

Description

Cosmetic or pharmaceutical compositions comprising at least hyaluronic acid, a Kakadu plum extract and thermal water from the Herculane spring. FIELD OF THE INVENTION

The present invention relates to the preparation of cosmetic or pharmaceutical compositions having an anti-aging effect.

STATE OF THE ART

Aging, particularly of the skin, is a multifactorial phenomenon. For example, we can cite the harmful action of free radicals, particularly oxygenated ones, on the structures and metabolism of the skin. These oxygenated radical species can also form in the skin due to the action of solar radiation (and more particularly UV rays) on it or by atmospheric pollution or even by inflammatory phenomena such as fever or taking certain medications.
These oxygenated radical species can also have an endogenous origin: in fact, cellular respiration by mitochondria produces free radicals that are toxic to the unsaturated fatty acids of the cell walls (oxidized fatty acids are no longer available for various important metabolisms), toxic to structural proteins (collagens, elastin) leading to their rigidification, toxic to enzymes by denaturing them and which are therefore inactivated, and finally toxic to DNA on which they can produce mutations that can either inactivate protein production or produce non-compliant proteins, sometimes deviant ones such as certain oncogenes (Borel 1984, Buechter 1988). However, it is known that in human cells, the quantity of oxidized proteins increases exponentially with age.

Oxygen radical species produced in the skin by exposure to light, whether solar or artificial, produce the same damage. However, we know that, in particular, type A UV rays penetrate quite deeply into the skin, down to the dermis, which is then subject to this damage.

The skin is not without possibilities to combat these phenomena, notably 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.

But these internal protections can be overwhelmed in the event of severe aggression, weakening of the body, fatigue, taking certain medications, triggering a harmful cycle of aging, in particular by maintaining low-level chronic inflammation.

To try to break this harmful cycle, we can supplement the skin with Vitamin C by exogenous intake. This is a widespread practice for a long time in cosmetology. Especially since Vitamin C in the skin has another very important activity: it stimulates the synthesis of collagen 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 that stabilize it. But, we also know 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 with processes that preserve this protective environment.

The Kakadu plum (Terminalia ferdinandiana) also called Billygoat plum, Gubinge or Murunga, is a flowering plant of the Combretaceae family, found in Australia, widespread in the woods from the Kimberley to eastern Arnherm Land and particularly in the Kakadu region. Its fruit contains the highest amount of Vitamin C of all fruits, fifty to one hundred times higher than that of an orange, and other anti-radical molecules such as tocopherols and polyphenols (ellagic acid and chlorogenic acid). This high concentration is not abnormal when we know that this region is particularly sunny and that the plants that live there are subjected to high doses of UV rays, without being able to move to the shade. The ripe fruits are crushed into a puree which is purified to remove the solid parts and impurities. This purified puree is then freeze-dried using the standard processes of this technique which allows the water to be extracted cold without heating and therefore without significant denaturation of Vitamin C and other anti-radicals. This produces a dry extract which contains 50 to 80% by weight of vitamin C and which can be easily transported and stored. This extraction can be done by any other appropriate process which preserves its qualities.

Kakadu plum extract was used quickly after its commercial availability and this use is notably cited in patents EP 1981513 and EP 2944313. The supply of vitamin C by the topical application of Kakadu plum extract (Terminalia ferdinandiana) is therefore beneficial to the skin to fight against free radicals and skin ageing.

To be active in the skin, vitamin C must be captured and transported to where it is needed by a cell surface glycoprotein: Sodium-dependent Vitamin C Transporter Type1 (SVCT-1 ) . However, it turns out that Kakadu plum extract (Terminalia ferdinandiana) promotes the synthesis of this glycoprotein, which is very important for vitamin C metabolism.

Another manifestation of skin aging is the loss of elasticity, which is mainly due to the decrease in the dermis of the main supporting molecules such as collagen, elastin and glycosaminoglycans (GAGs). The extracellular matrix (ECM) refers to the set of matrix components in the intracellular space. The extracellular matrix is mainly synthesized by fibroblasts in the dermis and acts as an interstitial medium. It allows the contact of the dermis with the basal layer of the epidermis via the dermo-epidermal junction. The extracellular matrix is the reservoir of cytokines vital for cellular survival and adaptability, such as growth factors.

The extracellular matrix is mainly composed of proteins (collagens, 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 repetitions of specific disaccharides. Hyaluronic acid (HA) is the most abundant GAG. It is a non-sulfated GAG (it is the only GAG that is not), present in the form of sodium salt. It is formed by a repetition of a disaccharide of glucuronic acid and N-acetylglucosamine, linked together by alternating glycosidic bonds b-1,4 and b-1,3.

Hyaluronic acid is synthesized by fibroblasts using an enzyme linked to the plasma membrane (HA synthase). It is directly secreted into the intercellular space. Hyaluronic acid is an essential constituent of the extracellular matrix. Due to its remarkable physical properties, it plays a major role in the structure and organization of the dermis and thus helps ensure its firmness and elasticity. In addition, thanks to its water retention power, hyaluronic acid plays a vital role in regulating skin hydration.

It is observed that the HA content in the dermis and epidermis decreases with age. Mature skin experiences many 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.

Collagen is present in many organs, in different types. There are nearly 30 in the scientific literature. Type I collagen, the most abundant in the human body, is mainly present in the skin, scar tissue, tendons and some bone parts. Collagen is a protein present in the extracellular matrix, and it is synthesized by fibroblasts. Collagen is the supporting protein of the dermis. In aged skin, there is a decrease in its synthesis compared to young skin (Variani et al.). In addition, there is an increase in collagen degradation in aged skin, particularly by oxygenated radical species and collagenases, which are called Matrix Metallo Proteases (MMP) specific to collagen. It is therefore essential to stimulate the synthesis of collagen I, which represents approximately 80% of dermal collagen.

The epidermis is made up 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 coherence between the keratinocytes regulates the variation in water content, which varies continuously from about 80% in the dermis and the basement membrane to about 10% in the most superficial layers of the epidermis. These two proteins are therefore very important for the stability and water regulation of the epidermis. However, here again, we see a decrease in these proteins with age, with the consequences of a lower coherence of the epidermis, less undulation of the dermo-epidermal junction and dryness of the skin.

The contribution 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 epidermal keratinocytes and the synthesis of collagen I by dermal fibroblasts.

The hyaluronic acid used is manufactured by reproducing a natural phenomenon. Some lactic bacteria can produce hyaluronic acid, an essential constituent of their capsule. This extracellular production is a natural defense phenomenon against stress conditions. The chemical structure of the molecule produced by biotechnology is identical to that produced endogenously by human fibroblasts. In a first phase, the cells of the selected strain (not genetically modified) multiply on a substrate resulting from the fractionation of wheat. In the 2nd phase, the bacteria are placed in stress conditions, which causes them to synthesize hyaluronic acid. The bacteria and proteins are then separated from the hyaluronic acid by sterilizing filtration. The polymer obtained then undergoes hydrolysis which produces a hyaluronic acid of low molecular weight between 10 and 60 KDa, preferably between 20 and 50 kDa, in the form of 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%.

The thymus is an immune aging clock. It induces a cellular response thanks to T lymphocytes that mature in the thymus. It is a defense against pathogenic microorganisms and the development of cancer cells. The thymus undergoes involution from the age of 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 disorders. The immune system ages and becomes less effective as we age.

This decrease in the effectiveness of the immune system or another permanent source of irritation such as permanent fatigue, certain drug treatments or poor diet, lead to low-level but permanent inflammation. This chronic inflammation accentuates aging by unnecessarily mobilizing too many pro-inflammatory cytokines, Metalo-Proteinases (MMPs) which degrade the support proteins of the dermis and lead to excess energy expenditure. This chronic inflammation modifies the marking and therefore the expression of certain genes (as does chronic pain). This phenomenon is called inflam-aging. To combat skin aging, it is therefore necessary to reduce its level of inflammation, even if it is low but permanent.

The Herculane spring is located in Romania, in the valley of the Cerna River, between the Mehedinti Mountains to the East and the Cerna Mountains to the West; it is a preserved natural area and far from urban or industrial pollution. This area contains ancient forests and many other unexploited springs. The water comes from drilling from a great depth (about 2,000 meters), it is bacteriologically pure. This spring is the oldest spa in Europe and it was built by the Roman Emperor Traian in the year 102 and exploited since for its therapeutic properties. The water of this spring contains minerals at a rate of 2,500 milligrams per liter, in particular calcium, magnesium, zinc and small amounts of copper, manganese and, the anions being mainly bicarbonate. This water is known for its anti-radical and anti-inflammatory properties which have been confirmed by ex-vivo and clinical tests on humans.

Furthermore, there is document GR1009780 which concerns cosmetic preparations with an anti-ageing effect, such as serums and creams for the face and eyes, which comprise a mixture of low molecular weight hyaluronic acids, in combination with active plant extracts, such as pomegranate or grape or lupin or Kakadu plum whose vitamin C content is 100 times higher than that of an orange.

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 a Kakadu plum extract for treating and/or preventing the aging of biological tissues in a synergistic manner.

TECHNICAL PROBLEM

There are therefore many cosmetic compositions in the prior art for treating skin aging. However, none of these compositions can act sustainably on the signs of aging, and/or can restore/improve the structure of the skin naturally. There is therefore a real need to find new compositions that are capable of effectively treating skin aging and/or of sustainably improving the appearance of the skin, and/or that improve the structure of the skin.

DESCRIPTION OF THE INVENTION

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 of between 10 and 60 kDa, preferably between 20 and 50 kDa, an extract of Kakadu plum (Terminalia fernandiana) and thermal water from the Herculane spring.

The inventor has also surprisingly demonstrated that the effects obtained are visible and long-lasting. In particular, the inventor has demonstrated that the composition according to the invention advantageously allows a visible and long-lasting reduction in the signs and markers of aging, for example a reduction in wrinkles and fine lines, advantageously improving the appearance of the skin, which can advantageously appear younger, or more beautiful skin, for example brighter skin, more supple, firmer and also tighter skin.

More particularly, the present invention relates to cosmetic or pharmaceutical compositions intended to be applied to the skin and characterized by the fact that to prevent the main signs of skin aging, they preserve some of the essential elements of the epidermis and dermis, they regenerate elements of cohesion 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.

According to the present invention, Kakadu plum (Terminalia ferdinandiana) extract is prepared from a dry extract of Kakadu plum dissolved in a mixture of water and glycerin, preferably a water/glycerin mixture with a 1/1 ratio by weight.

According to the present invention, the cosmetic or pharmaceutical compositions comprise at least powdered hyaluronic acid with a molecular weight of between 10 and 60 kDa, preferably between 20 and 50 kDa, an extract of Kakadu plum (Terminalia fermandiana) consisting of dissolving the dry extract in a mixture of half water and half glycerin by weight such that the vitamin C is in a proportion of 20% by weight in this solution, and thermal water from the Herculane spring, and the mineral components of which are bicarbonate (from 100 to 150 mg per liter, calcium (from 150 to 200 mg/l), magnesium (from 3.5 to 4.5 mg/l), iron (from 300 to 340 micrograms per liter), zinc (from 100 to 150 µg/l), copper (from 20 to 30 µg/l), manganese (from 30 to 55µg/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 the essential fatty acids of the cell walls, structural proteins such as collagen and elastin, the numerous enzymes necessary for the metabolism of cells and tissues, DNA which will be able to continue its vital functions without being mutated and reduce chronic inflammation of the skin, which often increases all these deleterious effects.

According to the present invention, the cosmetic or pharmaceutical compositions comprise at least hyaluronic acid with a molecular weight of between 10 and 60 kDa, preferably between 20 and 50 kDa, an extract of Kakadu plum (Terminalia fermandiana) 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 and characterized by the fact 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 Tranporter 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.

According to the present invention, the cosmetic or pharmaceutical compositions comprise at least hyaluronic acid with a molecular weight of between 10 and 60 kDa, preferably between 20 and 50 kDa, an extract of Kakadu plum (Terminalia fermandiana) in water-glycerin solution dosed at 20% by weight in vitamin C and thermal water from the Herculane spring, characterized in that the synergistic effect of these three active ingredients regenerates the cohesion elements of the epidermis by stimulating the synthesis by the keratinocytes of the epidermis of the proteins ZO-1 and Occludin constituting the tight junctions between the keratinocytes and which are very important for the stability and water regulation of the epidermis.

According to the present invention, the cosmetic or pharmaceutical compositions comprise at least hyaluronic acid with a molecular weight of between 10 and 60 kDa, preferably between 20 and 50 kDa and an extract of Kakadu plum (Terminalia fermandiana) in water-glycerin solution dosed with 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.

According to the present invention, the cosmetic or pharmaceutical compositions comprise at least hyaluronic acid with a molecular weight of between 10 and 60 kDa, preferably between 20 and 50 kDa, an extract of Kakadu plum (Terminalia fermandiana) in water-glycerin solution dosed at 10 to 30% by weight in vitamin C, preferably at 20% by weight in 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 wrinkles and fine lines of the crow's feet which are important signs of skin aging and reduces its inflammation which can aggravate these harmful effects.

More particularly, according to the present invention, the cosmetic or pharmaceutical compositions comprise:

- hyaluronic acid with a molecular weight of 10 to 60 KDa, preferably 20 to 50 KDa,

- vitamin C, and

-a mineral aqueous solution comprising calcium, magnesium, iron, zinc, copper, manganese and bicarbonate.

More particularly, according to the present invention, the hyaluronic acid content represents from 0.1 to 1%, preferably from 0.3 to 0.5% by weight of the cosmetic or pharmaceutical composition.

More particularly, according to the present invention, vitamin C is a dry extract of Kakadu plum (Terminalia ferdinandiana) in water-glycerin solution.

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.

More particularly, according to the present invention, the content of

- calcium in the composition is from 0.5 to 10 mg, preferably from 0.75 to 5 mg,

- magnesium in the composition is from 5 to 100 μg, preferably from 7.5 to 80 μg,

- iron in the composition is from 1 to 10 μg, preferably from 1.5 to 6.8 μg,

- zinc in the composition is from 0.1 to 5 μg, preferably from 0.5 to 3 μg

- copper in the composition is from 0.05 to 1 μg, preferably from 0.1 to 0.6 μg

- manganese in the composition is from 0.05 to 2 μg, preferably from 0.15 to 1.1 µg,

- bicarbonate in the composition is comprised from 0.1 to 5 mg, preferably from 0.5 to 3 mg.

More particularly, according to the present invention, the mineral aqueous solution is Herculane thermal water.

More particularly, according to the present invention, the Herculane thermal water content represents from 5 to 20% by weight of the cosmetic or pharmaceutical composition.

More particularly, according to the present invention, the cosmetic or pharmaceutical composition 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,

- from 0.1 to 5% by weight of vitamin C provided by a dry extract of Kakadu plum (Terminalia ferdinandiana) in water-glycerin solution, and

- from 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 µg/l of iron,

- 100 to 150 µg/l of zinc

- 20 to 30µg/l of copper, and

- from 30 to 55µg/l of manganese.

The cosmetic or pharmaceutical compositions of the present invention further comprise active ingredients such as anti-dandruff agents, anti-microbial agents, nail care agents, oral hygiene agents, personal hygiene agents, lipid restoration agents, tanning agents, vitamins, bacterial extracts, single or multi-cellular algae extracts, anti-inflammatories, ceramides or pseudo-ceramides, a or b hydroxy acids, plant extracts, stem cell extracts, plankton extracts, extracts of revitalizing plants or plants living in extreme conditions, exopolysaccharides, polymeric sugars, extracts of recycling products.

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 words in the form of liquids, pastes, creams, emulsions, lotions, oils, gels, masks, solids, powders, sprays, aerosols or any other form conforming to cosmetic or pharmaceutical uses, presented in suitable containers such as flasks, bottles, pots, boxes, ampoules, capsules, pencils, stick holders or any other container suitable for cosmetic or pharmaceutical use.

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, water/oil/water or oil/water/oil multiple 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 pasty soaps, foaming solutions, or one of the preceding forms containing microcapsules, nanocapsules, liposomes.

The cosmetic or pharmaceutical compositions of the present invention may further comprise cosmetic or pharmaceutical adjuvants conventionally used as oily phase components, gelling agents, emulsifiers, electrolytes, humectants, sequestrants, emollients, moisturizing agents, film-forming agents, insoluble pigments, dyes, sunscreens, active ingredients or any other ingredient usually used in cosmetic or pharmaceutical compositions.

a) Oily phase . The oily phase of the compositions of the present invention may contain, for example and without this being limiting: 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, linoleic caprylic/capric triglyceride, succinic caprylic/capric triglyceride, silicone oils such as cyclomethicones, dimethicones and dimethiconols, fatty alcohols such as stearic alcohol, cetyl alcohol and hexadecyl alcohol, fatty acids such as glyceryl stearate, ... stearic acid, palmitic acid, fatty acid esters such as dioctyl succinate, glyceryl dioleate, myristyl myristate and isopropyl myristate, waxes such as beeswax, paraffin, carnauba wax, ozokerite, lanolin and its derivatives (oil, alcohol, waxes), and mixtures thereof.

In the cosmetic or pharmaceutical compositions of the present invention, the oily phase may represent from 0.1 to 100% by weight, and preferably from 0.25 to 50%, by weight of the composition.

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 fermentation of bacteria such as Xanthan gum, Sclerotium gum and Gellan gum, acrylic polymers such as carbomers, polyacrylates, polymethacrylates and their derivatives, quaternized polymers, PVPs and polymers derived from PVP and mixtures thereof. In the cosmetic or pharmaceutical compositions of the present invention, the gelling agent or the combination of gelling agents can represent from 0.1 to 30%, and preferably from 0.25 to 25%, by weight of the composition.

c) 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, and without limitation, 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, ethoxylated plant sterols or not, or a mixture of one or more of the emulsifiers mentioned above. The amount of emulsifiers optionally present in the 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.

d) Other components . The cosmetic or pharmaceutical compositions according to 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 ranging 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 ranging from 0.1 to 40% by weight of the composition, sequestrants such as tetrasodium EDTA, preferably in an amount ranging 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 ranging 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 an amount ranging from from about 0.01 to 20% by weight of the composition, film-forming agents to facilitate spreading on the surface of the skin, such as hydrolysates of oat, wheat, collagen and almond proteins, preferably in an amount ranging from about 0.1 to 5% by weight of the composition, insoluble pigments such as titanium oxide, rutile titanium oxide, anatase titanium oxide, pyrogenic titanium oxide, micronized titanium oxide, titanium oxide surface-treated with silicones or with amino acids, or with lecithin, or with metal stearates, iron oxides, iron oxides surface-treated with silicones, or with amino acids, or with lecithin or with metal stearates, zinc oxide, micronized zinc oxide, mica coated with titanium oxide, preferably in an amount ranging from from about 0.5 to 10% by weight of the composition and their mixtures, water-soluble or fat-soluble dyes, fixed or not on supports (lakes), such as CI 19140, CI 42090, CI 40800, for the 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 according to the country, active ingredients intended to enhance the activity of cosmetic or pharmaceutical products in other areas of skin care and its annexes, such as, for example, and without this being limiting, anti-dandruff, anti-microbial agents, nail care, oral hygiene, intimate hygiene, lipid restoration agents, tanning agents, vitamins such as Vitamins A, C, E, bacterial extracts, single or multi-cellular algae extracts, 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 licorice extracts, Centella asiatica, Boswellia serrata, vine shoot, soy, Saw palmetto, Epilobium roseum, Angelica sinensis, Dioscorea villosa, apple, Lepidum peruvianum, Actea racemosa, Salix alba, Canlendula officinalis, Ginseng, Sophora japonixa, Eucalyptus macrorrhyncha, Gingko biloba, passiflora incarnata, Silibum marianum, Helichrysum stoechas, Green tea, Achillea millefolium, extracts of stem cells from various plants, extracts of plankton, of revitalizing plants or plants living in extreme conditions such as Myrothamus flabellifolia, Rhodiola serrulata, Chapparal, 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 b-poly-b-1-3 glucopyranose extracted from yeast membranes, extracts of recycling products such as vine shoots vine, orange or tangerine peels after extraction of their juice.

The cosmetic or pharmaceutical compositions of the present invention may further contain preservatives, antiperspirants, antistatics, whitening agents, buffers, thickening agents, chelating agents, depilatories, detangling agents, foaming agents, masking agents, opacifiers, pearlescent agents, plasticizers, propellants, refreshers, solvents or any other agent suitable for cosmetic or pharmaceutical use.

All these active ingredients or complementary agents can be incorporated into the cosmetic or pharmaceutical compositions of the present invention, in proportions of 0.001 to 50% and their list is in no way limiting.

In all that follows or precedes, percentages are given by weight unless otherwise stated.

EXPERIMENTAL PART

Example 1

Anti-radical effect test .

Diphenylpicrylhydrazyl (DPPH) is a free radical scavenger that is used to measure the free radical scavenging activity of a substance by its ability to scavenge DPPH free radicals. A triplicate test was carried out with Kakadu plum extract in hydro-glycolic solution at 20% of vitamin C tested at 1% in distilled water (referred to as 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 (referred to as HA bpm 0.5), the mixture of the two previous ones and Herculane thermal water diluted at 5% in distilled water and, finally, the mixture of Kakadu plum extract in water-glycerin solution at 20% of vitamin C at 1%, 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).

Active tested Anti-radical effect at 30 mins Anti-radical effect at 24 hours K 1 +54%+/- 2% +69%+/-2 HA bpm 0.5 +22= :-0.5% +29%+/-1% K1 + HA bpm 0.5 102+/-2% 135+/-2% Herculane thermal water 5% +5%+/-0.5% +8%+/-0.5% Blend 122%/-2% +152%+/-2%

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 synergistic anti-radical effect.

Example 2

Sodium-dependent Vitamin C Transporter Type-1 (SVCT-1) receptor synthesis stimulation test.

The test is performed in triplicate on human keratinocyte cultures. The concentrations of the active ingredients in distilled water are reduced compared to the concentrations used in a complete cosmetic product, because they are in direct and immediate contact with epidermal cells, whereas, when they are in a complete cosmetic product, the contact is made after dilution in the stratum corneum and then the other layers of the epidermis, which makes a significant dilution before there is contact with living cells. To determine the optimal concentrations to use in such an in vitro test, the maximum concentration of each active ingredient that does not alter the cells used in the test is first determined. Iron chloride (FeCl3) at 10 mM was used as a positive control. The synthesis of SVCT-1 was measured by ELISA after 24 hours. The results are expressed as a percentage increase in the synthesis of the SVCT-1 receptor compared to the control condition (without addition of active ingredient). The active ingredients tested are Kakadu plum extract in water-glycerin solution with 20% vitamin C and tested at 0.1% in distilled water (called K 0.1), hyaluronic acid powder with a molecular weight of 20 to 50 KDA tested at 0.05% in distilled water (called 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 water-glycerin solution with 20% vitamin C at 0.1%, hyaluronic acid bpm at 0.05% and Herculane thermal water at 8% (called Mixture) in distilled water. The results are summarized in Table 2:

Active 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% Blend +158%+/-1.4%

In this test we also 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 synergistic anti-radical effect.

Example 3

Test for stimulation of keratinocyte synthesis of ZO-1 and Occludin proteinsconstitutive of the tight junctions between keratinocytes in the epidermis. These two proteins are very important for the stability and water regulation of the epidermis. The test was performed on normal human keratinocytes from plastic surgery. They were seeded in 12-well plates in appropriate culture medium and incubated for 24 h. After incubation, the culture medium was renewed with medium containing or not the products to be tested. The cells were then incubated for 72 h at 37 ° C under a 5% carbon dioxide atmosphere. The experiment was conducted in triplicate for each condition.

Membrane proteins are extracted with an appropriate buffer and then deposited at 3.6 µg/well and separated on a suitable electrophoresis gel.

After migration, the proteins are transferred to a nitrocellulose membrane, which is saturated with an appropriate 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 revealed, after incubation for one hour at room temperature and washing, using a second antibody conjugated to peroxidase. The activity of the peroxidase is revealed by chemiluminescence. Here again, the maximum concentrations are determined in advance for each active ingredient, so that there is no interference with the viability of living cells. The active ingredients tested are Kakadu plum extract in water-glycerin solution at 20% of vitamin C tested at 0.2% in distilled water (called K 0.2), hyaluronic acid powder with a molecular weight of 20 to 50 KDa tested at 0.1% in distilled water (called 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% of 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 Mixture). The results expressed in quantities of proteins synthesized are summarized in Table 3:

Active tested ZO-1 Occludin Witness 100 100 K 0.2 129 139 Herculane thermal water 10% 12
25 HA bpm 0.1 110 105 Blend 296 303

We also see here that the mixture of the 3 active ingredients gives a biological activity greater than the sum of the results of the active ingredients alone, and that, therefore, the mixture of these active ingredients is synergistic in stimulating the synthesis of the proteins ZO-1 and Occludin by normal human keratinocytes, proteins important for the regulation of the hydration of the upper layers of the epidermis and useful in combating skin aging.

Example 4

Pro-Collagen I synthesis stimulation test .

The test was performed on normal human fibroblasts from plastic surgery. They were seeded in 12-well plates in appropriate culture medium and incubated for 48 h in the presence of the test products.

Keratinocytes synthesize pro-Collagen I, which, in the skin, will be used to produce Collagen I. In the test, the supernatants containing the pro-Collagen are collected, stored at -20°C and then tested with a specific kit.

Vitamin C is also tested as a positive control for the synthesis of pro-Collagen I, at a dose of 5 mg/ml. Kakadu plum extract in a water-glycerin solution with 20% vitamin C and tested at a dose of 5 mg/ml (called 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 (called HA bpm 5 mg/ml), Herculane thermal water diluted to 20% in distilled water and the mixture of these last three active ingredients at the same doses are also tested. The results are shown in Table 4:

Active tested Relative stimulation of procollagen I synthesis Vitamin C positive reference control 100 Distilled water negative control 0 Kakadu Plum Extract 5mg/ml 90 HA bpm 5 mg/ml 121 Kakadu plum extract 5mg/ml + HA bpm 5mg/mil 255 Herculane thermal water 20% 10 Blend 272

We see that the Kakadu plum extract, which contains 20% by weight of vitamin C, stimulates the synthesis of procollagen I almost as much as pure vitamin C. The action 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 the three active ingredients is even superior, which once again demonstrates the synergistic effect of this mixture.

Example 5

Test on release histamine on human skin explants.

Neurogenic inflammation causes skin irritation due to a local release of neuropeptides including substance P. This neurotransmitter is in fact one of the factors responsible for the inflammatory response. Substance P acts directly on the vascular wall causing edema, vasodilation and degranulation of mast cells with release of histamine (Eur.J. Dermatol 1995;5:349-357). The possible soothing effect of an active ingredient on the release of histamine can be tested in a model of human skin explants stimulated or not with substance P. The test was carried out with healthy skin explants of human origin of 8 mm in diameter and which were obtained from surgical abdominoplasties of 2 donors, one aged 32, the other 63 years old. They are placed in 24-well plates and left to stabilize in an incubator at 37°C, 5% _CO2 for 4 hours in an appropriate survival medium.

After application of substance P (at 1 µM in phosphate buffered saline PBS without calcium) for 1 hour, the supernatants are collected and histamine is measured with an ELISA kit.

The explants 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 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 the mixture of these 3 active ingredients at the same doses in distilled water. The results are expressed in the quantity of histamine released and are summarized in the following table:

Active 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 at 1% 7.1 5.5 Kakadu Plum Extract 3% + HA bpm 1% 4.8 4.9 Herculane thermal water at 20% 4 ;4 25 Mix of the 3 1.5 1.8

We see that the mixture of the 2 active ingredients Kakadu plum extract and hyaluronic acid bpm 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 quantity of histamine released by substance P, hence a powerful anti-inflammatory effect.

Example 6.

Cosmetic cream prepared with the 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:

Arachidyl Alcohol & Behenyl Alcohol & Arachidyl Glucoside 4g

Jojoba Oil 4g

Caprylic/Capric Triglycerides 4g

Jojoba Esters 1g

Hydrogenated Polyisobutene 4g

Isocetyl Stearate 4g

Cetyl ricinoleate 4g

Shea Butter 1g

Dipentaerythrityl Hexacaprylate/Hexacaprate 3g

This mixture is brought to 70°C and well homogenized.

In addition, the following aqueous phase is prepared:

Purified water Q.S.100

Herculane thermal water 20g

Tetrasodium EDTA 0.05g

Glyceryl Polymethacrylate/Propylene Glycol 5g

Cellulose 2g

Silica beads coated with metal oxides 1g

Sodium Acryloyldimethyltaurate Copolymer & Isohexadecane & Polysorbate 80 1.25g

All the ingredients of the aqueous phase are dissolved in water and the whole is brought to 70°C. The fatty phase, homogeneous and heated to 70°C, is poured slowly onto the aqueous phase brought to the same temperature, with fairly vigorous stirring. Stirring is continued for 10 minutes after the end of the introduction of the fatty phase. The oil-in-water emulsion is formed.

Then the emulsion is cooled with moderate stirring.

When the temperature reaches 40°C, add successively with moderate stirring:

Hyaluronic acid powder molecular weight 20 to 50 KDa 0.3g

Kakadu plum extract 20% vitamin C 0.5g or 0.2g vitamin C

Preservatives 0.15g

Perfume 0. 3g

After homogenization, the emulsion is cooled to 30°C with slow stirring.

This produces a white emulsion with a pleasant consistency, suitable for mature skin that tends to become dry, rough, with less firmness and with the appearance of wrinkles and fine lines.

Example 7. Anti-aging Oil/Water Emulsion

The fatty phase is made up of:

Caprylic/Capric Triglycerides 8g

Isodecyl Neopentanoate 5g

Hydrogenated Polyisobutene 5g

Jojoba Oil 5g

Cetyl Alcohol 1g

Stearic Acid 1g

Beeswax 1g

Glyceryl Stearate 0.5g

This fatty phase is heated to 70°C and well homogenized.

In addition, the following aqueous phase is prepared:

Purified water Q.S.100g

Herculane thermal water 5g

Tetrasodium EDTA 0.05g

Glycerin 3g

Sorbitol 2g

Carbomer 0.25g

Xanthan Gum 0.2g

Biosaccharide Gum-1 0.5g

Polyethylene Glycol 400 2g

Preservatives 0.5g

10% soda 0.5g

All the ingredients of the aqueous phase are dissolved in water and the whole is brought to 70°C.

The fatty phase, homogeneous and heated to 70°C, is slowly poured onto the aqueous phase brought to the same temperature, with fairly vigorous stirring. Stirring is continued for 10 minutes after the end of the introduction of the fatty phase. The oil-in-water emulsion is formed.

Then continue vigorous stirring for at least 10 minutes.

Then the emulsion is cooled with moderate stirring.

When the temperature reaches 40°C, add successively with moderate stirring:

Hyaluronic acid powder molecular weight 20 to 50 KDa 0.1g

Kakadu plum extract with 20% vitamin C 0.5g or 0.2g of vitamin C

Perfume 0.35g

After homogenization, the emulsion is cooled to 30°C with slow stirring.

The result is a white, creamy cream with a very fresh feel, to combat the effects of aging such as dry skin, loss of radiance and firmness, the appearance of a certain roughness and wrinkles and fine lines.

Example 9. Oil/Water emulsion with lamellar phases for the face and body

The fatty phase is made up of:

Cetearyl Alcohol & Cetearyl Glucoside 6g

Octyl Stearate 2g

Beeswax 1.5g

Propylene Glycol Dicaprylate/Dicaprate 2.5g

Jojoba Oil 4g

Shea Butter 4g

This fatty phase is heated to 80°C and well homogenized.

In addition, the following aqueous phase is prepared:

Purified water Q.S.100g

Herculane thermal water 20g

Tetrasodium EDTA 0.05g

Glyceryl Polymethacrylate & Propylene Glycol 10g

Preservatives 0.5g

All the ingredients of the aqueous phase are dissolved in water and the whole is brought to 80°C.

The fatty phase, homogeneous and heated to 80°C, is slowly poured onto the aqueous phase brought to the same temperature, with fairly vigorous stirring. Stirring is continued for 10 minutes after the end of the introduction of the fatty phase. The oil-in-water emulsion is formed.

Then the emulsion is cooled with moderate stirring.

When the temperature reaches 40°C, add successively with moderate stirring:

Hyaluronic acid powder molecular weight 20 to 50 KDa 1g

Kakadu Plum Extract 20% Vitamin C 2.0g or 0.4g Vitamin C

Perfume 0.35%

After homogenization, the emulsion is cooled to 30°C with slow stirring.

A very creamy white cream is obtained, with lamellar phases, which can facilitate the penetration of active ingredients and prolonged hydration. It is perfectly suited for facial and body care and in particular to increase the radiance, the glow of the skin, reduce its roughness, reduce the total length of wrinkles and fine lines of the crow's feet and restore the firmness of the skin.

Example 10 : treatment foundation.

We prepare the following fatty phase:

Cetyl Alcohol 1g

Glyceryl Stearate 2g

Stearic Acid 1g

Tocopherol acetate 0.5g

Jojoba Oil 3g

Perfluoro Polymethyl Isopropyl Ether 0.5g

Cetearyl Octanoate 6g

Diisostearyl Malate 8g

This fatty phase is heated to 80°C and well homogenized.

In addition, the following aqueous phase is prepared:

Purified water Q.S.100g

Herculane thermal water 15g

Tetrasodium EDTA 0.05g

Xanthan gum 0.3g

Preservatives 0.6g

All the ingredients of the aqueous phase are dissolved in water and the whole is brought to 80°C. The fatty phase, homogeneous and heated to 80°C, is poured slowly onto the aqueous phase brought to the same temperature, with fairly vigorous stirring. Stirring is continued for 10 minutes after the end of the introduction of the fatty phase. The oil-in-water emulsion is formed.

Then add the pigments and talc and mix vigorously while hot:

Titanium Oxide 6.3g

Mixture of yellow iron oxide and talc 4.1g

Mixture of red iron oxide and talc 0.2g

Mixture of Brown Iron Oxide and Talc 1.5g

Talc 5g

When the colored emulsion is perfectly homogeneous, begin cooling with moderate stirring.

After good homogenization and when the temperature reaches 40°C, add with moderate stirring:

Hyaluronic acid powder molecular weight 10 to 60 KDa 1.0g

Kakadu plum extract 20% vitamin C 5g or 1g of vitamin C

Perfume 0.35g

After homogenization, the emulsion is cooled to 30°C with slow stirring.

We obtain a foundation for makeup treating wrinkled and dull skin.

Example 11

Clinical test to validate the synergistic action on the skin of the mixture of Kakadu plum extract with 20% vitamin C dosed at 2% or 0.4g of vitamin C, hyaluronic acid with a molecular weight between 20 and 50 kDa dosed at 1% and Herculane thermal water dosed at 20% introduced into the cosmetic cream of example 9.

The test is carried out on 88 female volunteers of phototype I to IV, aged between 35 and 65 years (average age 48 years), who have dry skin, wrinkles and fine lines at the crow's feet, more or less rough skin and fairly dull skin. The people do not have psoriasis, eczema, erythema, edema, scars or lesions of any kind on the face. The people have not started, changed or stopped hormone replacement therapy during the last three months before the start of the test or during the duration of the test. The people have not applied an anti-wrinkle product (for example based on a-hydroxy acids, fruit acids or retinol) for at least two weeks before the start of the test. Individuals agree not to use any facial cosmetic products other than the product being tested during the test, except for makeup removers, toners or makeup without skincare claims.

Individuals agree not to use, during the test, any medication containing aspirin, steroidal or non-steroidal anti-inflammatories, or DHEA (only limited use of paracetamol is permitted).

No cosmetic product (including the product to be tested) may be used on the areas studied on the measurement days.

The volunteers are divided into 5 groups of 22 volunteers each, homogeneous groups for all the above criteria. The cream is prepared according to the formula of Example 9, and 10 other creams modified as follows: a placebo cream or Kakadu plum extract with 20% vitamin C, 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 20% vitamin C dosed at 2% by weight, a cream containing only hyaluronic acid powder with a molecular weight of 20 to 50 KDa dosed at 1% by weight, a cream containing Kakadu plum extract with 20% vitamin C dosed at 2% by weight, and hyaluronic acid with a molecular weight of 20 to 60 KDa dosed at 1% by weight, and finally a cream containing 22% by weight of Herculane thermal water. The application of all these 5 creams is done on half of the face twice a day for 30 days.

For skin radiance, radiance is measured by spectrometry/colorimetry on D0 and D30.

Roughness is assessed for each volunteer by a Dermatologist according to the scale described in Table 6:

Score Skin condition 0 Smooth skin 1 Very slightly rough skin 2 Slightly rough skin 3 Moderately rough skin 4 Very rough skin

The amounts to be used are those that people usually use for this type of product on their face.

This is an open study: the investigators and the people tested are aware of the objective of the study. This is a non-comparative study. Each person is their own reference on day D0. The method applied is that of silicone replicas on the goose foot. The selection of the goose foot to be measured is randomized using specific software.

People must arrive for the measurements without any makeup or cosmetic products on their face. After 15 minutes of acclimatization at 21°C plus or minus 1°C, humidity 45% plus or minus 5%, people are placed in a semi-reclining position in a suitable chair. The positioning of the subjects is the same from one measurement to another thanks to hollow marks in the backrest.

The crow's feet prints are made with 8g of silicone resin (Silflo, Flexico Developments Ltd, Great Britain) mixed with 8 drops of catalyst using a spatula. An imprint of the entire crow's feet is made. This includes 5 cm from the corner of the eye to the edge of the hair, at least 3 cm towards the eyebrow and forehead and at least 3 cm towards the cheek. During the taking of the print, the person's eye remains open, and the head is straight. After 10 minutes, the print is detached from the skin. On the back of the print, the person's number, the side studied and the date of the measurement (D0 and D30) are noted. The prints are studied by the cast shadow method which allows to measure the total length of wrinkles and the total area of wrinkles in the area considered. The evolution of these parameters can therefore be measured between the start of the test (D0) and the end of the test (D30). Skin firmness is measured using a Cutomètre® which is designed to measure the biomechanical properties of the upper layers of the epidermis by applying negative pressure (suction) which deforms the skin. The measurement principle is based on the suction method. A negative pressure is created in the device and the skin is sucked into the measuring cup of the probe. After a defined time, the skin is released inside the probe. The penetration depth is determined by a non-contact optical measuring system. This optical measuring system consists of a light source and a light receiver. The intensity of the light varies depending on the depth of penetration of the skin. The skin's resistance to negative pressure (firmness) and its ability to return to its original position (elasticity) are displayed as curves (penetration depth in mm/time unit) in real time during the measurement. This measuring principle provides information on the elasticity and mechanical properties of the skin surface.

The results of all these tests are summarized in Table 7.

Result at D30 compared to D0 Radiance, skin glow Roughness of the skin Total length of crow's feet lines and wrinkles Skin firmness with Cutomètre® Group 1 Placebo-treated side -0.4% -0.6% -2% +2% Group 1 Treated side Kakadu plum extract 2% +17% -11% -12% +15% Group 2 Placebo-treated side -0.3% -0.5% -1.8% +2.5% Group 2 Treated side HA bpm 1% +12% -12% -13% +17% Group 3 Placebo-treated side -0.4% -0.8% -1.5% +1.2% Group 3 Treated side 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 a mixture of Kakadu plum extract and hyaluronic acid +34% -26% -29% +36% Group 5 Placebo-treated side -0.3% -0.5% -1.8% +1.5% Group 5 Side treated with complete mixture +45% -35% -43% +49%

As for the results obtained in vitro and ex vivo previously described, the clinical test on humans with measurements carried out on several significant criteria of the state of the skin, shows that the action of a Kakadu plum extract with 20% vitamin C dosed at 2% or hyaluronic acid powder with a molecular weight of 20 to 50KDa dosed at 1% or Herculane thermal water dosed at 22% have beneficial effects on the skin of volunteers after 30 days of application twice a day (radiance, skin radiance, skin roughness, total length of wrinkles and fine lines of the crow's feet, skin firmness) and especially that the mixture of the first two active ingredients gives results surprisingly superior to the addition of the results of the creams containing only one of the two active ingredients, in comparison of each volunteer compared to half of the face that received the placebo cream (without any of the three active ingredients). And that the addition of Herculane thermal water further reinforces all these synergistic results in clinical testing on human skin.

Claims (13)

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, and
-a mineral aqueous solution comprising calcium, magnesium, iron, zinc, copper, manganese and bicarbonate. 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. Composition according to claim 1 characterized in that the vitamin C is a dry extract of Kakadu plum (Terminalia ferdinandiana) in water-glycerin solution. Composition according to claim 1 characterized in that the vitamin C content represents from 0.1 to 5% by weight of the composition. Composition according to claim 1 characterized in that the content of
- calcium in the composition is from 0.5 to 10 mg, preferably from 0.75 to 5 mg,
- magnesium in the composition is from 5 to 100 μg, preferably from 7.5 to 80 μg,
- iron in the composition is from 1 to 10 μg, preferably from 1.5 to 6.8 μg,
- zinc in the composition is from 0.1 to 5 μg, preferably from 0.5 to 3 μg
- copper in the composition is from 0.05 to 1 μg, preferably from 0.1 to 0.6 μg
- manganese in the composition is from 0.05 to 2 μg, preferably from 0.15 to 1.1 µg,
- bicarbonate in the composition is comprised from 0.1 to 5 mg, preferably from 0.5 to 3 mg. Composition according to claim 1 characterized in that the aqueous mineral solution is Herculane thermal water. Composition according to claim 6, characterized in that the Herculane thermal water content represents from 5 to 20% by weight of the composition. 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,
- from 0.1 to 5% by weight of vitamin C provided by a dry extract of Kakadu plum (Terminalia ferdinandiana) in water-glycerin solution, and
- from 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 µg/l of iron,
- 100 to 150 µg/l of zinc
- 20 to 30µg/l of copper, and
- from 30 to 55µg/l of manganese. Composition according to one of the preceding claims, characterized in that it further comprises active ingredients such as anti-dandruff agents, anti-microbial agents, nail care agents, oral hygiene agents, personal hygiene agents, lipid restoration agents, tanning agents, vitamins, bacterial extracts, single or multi-cellular algae extracts, anti-inflammatories, ceramides or pseudo-ceramides, a or b hydroxy acids, plant extracts, stem cell extracts, plankton extracts, extracts of revitalizing plants or plants living in extreme conditions, exopolysaccharides, polymeric sugars, extracts of recycling products. Composition according to one of the preceding claims, characterized in that it further comprises oily phase components, gelling agents, emulsifiers, electrolytes, humectants, sequestrants, emollients, moisturizing agents, film-forming agents, insoluble pigments, dyes, sunscreens, preservatives, antiperspirants, antistatic agents, whitening agents, buffers, thickening agents, chelating agents, depilatories, detangling agents, foaming agents, masking agents, opacifiers, pearlescent agents, plasticizers, propellants, refreshers, 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. Composition according to 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, pots, boxes, ampoules, capsules, pencils, stick holders or other suitable containers, in particular oil/water or water/oil emulsions, twin-phase emulsions, microemulsions, PIT emulsions, nanoemulsions, water/oil/water or oil/water/oil multiple emulsions, pseudoemulsions (dispersion 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 pasty soaps, foaming solutions, or one of the preceding forms containing microcapsules, nanocapsules, liposomes Cosmetic treatment process, advantageously for combating oxidative stress, and in particular cellular aging of the skin, consisting of applying to the skin the cosmetic composition according to one of claims 1 to 10. Use of a composition according to one of the preceding claims for:
- a synergistic anti-radical action preserving the essential elements of the epidermis and dermis,
- a synergistic action of stimulation of the synthesis of the SVCT-1 receptor (Sodium-dependent Vitamin C Transporter Type-1) on keratinocyte cultures measured by ELISA , this stimulation reinforcing the anti-radical action of the association of the three active ingredients,
- a synergistic action of stimulation of the synthesis by keratinocytes of the proteins ZO-1 and Occludin constituting the tight junctions between the keratinocytes in the epidermis, and reinforces the cohesion of the epidermis and ensures its water regulation,
- a synergistic action of stimulation of the synthesis of pro-collagen I by the fibroblasts of the dermis and thus regenerates the support elements of the dermis promoting the increase in firmness, suppleness and elasticity of the skin, and
-a synergistic action of improving skin radiance and brightness, skin roughness, skin firmness and a synergistic action of reducing the total length of crow's feet wrinkles and fine lines in clinical testing on human volunteers.
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