HK1192152B - Novel anti-redness active agent and compositions comprising same - Google Patents

Description

The present invention relates to the prevention and treatment of redness of the skin, which is often considered unsightly. It relates to the use of arabinogalactane and compounds containing it for the prevention and treatment of redness. A particularly effective compound for redness of the skin includes arabinogalactane and lupin peptides. A method for the prevention and/or treatment of redness of the skin is presented, including the administration to a person with redness of the skin of a compound containing arabinogalactane.

The Commission has

Redness of the skin is a skin disorder, mainly present on the face, which can have various origins. It can be short-term (flushes) or permanent. Secondary criteria can manifest as burning sensations, tingling, red patches, dry skin, facial edema. Depending on the severity of these rednesses, the aesthetic disability can be very intense and be accompanied by disastrous social consequences. It is estimated that 10% of the European population is affected.

People with redness usually have an abnormal sensitivity to the environment and to many factors, such as: hot drinks, alcohol, temperature changes, spicy foods, exercise, stress and strong emotions, sun exposure, and so on.

The cause of these redness is not well known and is multifactorial: it involves genetic, inflammatory and vascular factors.

Recently, Gallo's team discovered [1] and highlighted the involvement of an altered innate immune response in the initiation of skin disorders, and proposed several molecular mechanisms and key interconnected actors in the onset of redness: 1) altered innate immunity; 2) vascular disorders; 3) microbes; 4) oxidative stress and sun.

1- Dysregulation of the innate immune response

The innate immune system involves a recognition system including Toll-Like Receptors (TLRs), which are capable of responding to many environmental stimuli such as UV, microbes, physical or chemical aggression. Following the recognition stage, the innate immune response sets in with a controlled production of mediators such as cytokines and antimicrobial peptides (AMPs). Among the AMPs, LL37 cathelicidins have antimicrobial properties, but are also involved in scarring and in initiating the immune response acquired by chemotactic properties. To release the active form of cathelicidine LL37, the pro-form must be encoded by a type of enzyme called serine or calcitonin tryptophanase 5 (SCTE).

In biopsies of subjects with redness (particularly due to dilation of superficial blood vessels at the skin surface), the amount of LL37 cathelicidins is greatly increased. Compared to normal skin, LL37 cathelicidins are not only present in more abundant amounts but have a different peptide profile, therefore these cathelicidins are called LL37 variants. These LL37 variants exhibit vasoactive and pro-inflammatory properties by inducing the production of IL8 and certain pro-angiogenic mediators [2,3]. The presence of these LL37 variants in significant amounts in red skin disorders is considered important because they could play an important role in the production of the matrix protein kallikase 5K, which is involved in the production of mature cells such as calcium and calcium-like fatty acids (calcium and calcium-like fatty acids) and in the production of certain inflammatory cells such as calcium and calcium-like fibrils (calcium and calcium-like fatty acids) [4].

This was confirmed experimentally by injecting the LL37 peptides or KLK5 enzyme into the skin of mice inducing skin inflammation (erythema, vasodilation) mimicking changes seen in erythrocouperosis [5].

The same team has just shown that TLR2 receptor expression is abnormally increased [6], this increasing susceptibility to certain stimuli and leading to increased production of kallikreins and cathelicidins and thus an exacerbated response that the same stimuli would not have induced in normal subjects.

2- Vascular disorders

Many people have episodic flushes; this leads to the hypothesis of vascular hyper-reactivity that plays a major role in this unsightly phenomenon. A few studies show increased blood flow in skin lesions of subjects with skin flushes.[8] Factors that trigger these flushes such as emotional stress, spicy food, hot drinks, high environmental temperatures, and menopause, exacerbate the appearance of the flushes and support the vascular theory.[8]

Erythrocouperosis refers to the presence of redness on the surface of the skin associated with small capillaries mainly located in the face or sometimes the neck. There is undeniably neoangiogenesis (neovascularization or synthesis of new blood vessels) in the appearance of these redness, resulting in telangiectasias (small apparent vessels).[9] The initial stimulus remains unknown, although sunlight or other environmental factors are suggested candidates to cause this phenomenon.

Repeated vasomotor reactions cause damage to the lymphatic system, causing persistent inflammation that is bothersome to the person.

This induces the activation of cells capable of producing pro-inflammatory molecules, angiogenic growth factors such as VEGF or FGF2 and proteases such as metalloproteinases or MMPs. MMPs break down the extracellular matrix of skin tissue and thereby release angiogenic growth factors, and degrade the vascular walls allowing endothelial cells to migrate.[10] Neoangiogenesis involves the formation of new vessels from existing vessels via morphological and functional changes of vascular endothelial cells.

In addition, cathelicidins may also be a trigger for hypervascularity and angiogenesis in the development of skin redness [5, 13].

The key steps of angiogenesis are: → Release of deleterious mediators from the environment by cells: cytokines, proteases such as MMPs, and proangiogenic growth factors;→ The balance shifts in favour of proangiogenic mediators: VEGF/FGF2 (or bFGF) which are: Secretion by environmental cells,Release from the extracellular matrix by MMPs;→ Activation of endothelial cells→ Degradation of the vascular wall by MMPs→ Migration and proliferation of endothelial cells→ Formation of new vessel

In the appearance of redness, sun exposure, oxidative stress, and certain microbes are factors that trigger and exacerbate the unsightly phenomenon.

3- The role of bacteria and parasites

Demodex folliculorum is a saprophyte (mites) parasite that colonizes the hair follicle and may increase in density during skin rashes. A bacterium Bacillus oleronius has been isolated from Demodex : 1 parasite contains 40 bacteria. This bacterium B. oleronius induces proliferation of mononuclear cells and causes an inflammatory response in people with pustule-associated rashes. In addition, B. oleronius releases molecules that stimulate innate immunity via TLRs.

4- Oxidative stress and sunlight

The cell source of ROS is thought to be leukocytes and keratinocytes. Following the release of ROS, a cascade of cellular signals is set up to induce the production of pro-inflammatory mediators (TNFα by keratinocytes) and MMPs (by fibroblasts). Thus, ROS contribute to damage of dermal and vascular material and inflammatory response.

UV causes flushes and aggravates skin redness. UV induces angiogenesis in mice and stimulates the production of VEGF, FGF2 in keratinocytes and mouse skin. UV also generates ROS and stimulates the production of inflammatory mediators (IL8) and MMPs. UV stimulates the TLR2 pathway and in particular induces the production of LL37. UV qualitatively and quantitatively alters the dermal connective tissue that is the support of the vascular network.

Previous art

Few compounds are known to prevent and/or treat skin redness. Hemp oil is known to alleviate symptoms. In case of a bacterial attack, antibiotic creams may be prescribed. Topical steroids may have a short-term effect, but in the long term they tend to worsen cutaneous symptoms. Laser treatment can destroy the superficial vessels of the patient's epidermis for a few years: this expensive treatment, however, must be repeated regularly.

Compounds containing chitosan and a short/medium chain dicarboxylic acid amide, forming a film upon application to the skin, have been described for the prevention and treatment of skin redness (WO 2009/150257).Pituitary adenylate cyclase activating polypeptide (PACAP) receptor modulators have also been proposed to reduce skin redness (WO 2010/007175).Herbal compounds have also been described, such as: Compounds containing green tea and/or soybean extracts in combination with extracts of ginkgo bilboa leaves (FR2885301);Compounds containing caffeine (FR2855050);Compounds containing lupin peptides which have metalloprotease inhibitory properties (WO 00/62789).

The Arabinogalactans

Arabinogalactans (also called galactoarabinanes) are polysaccharides. They are found in varying amounts in many plants, fungi, and bacteria. Arabinogalactans are naturally soluble fibers that can be extracted from bacteria or plants such as coffee or lettuce.

Arabinogalactane is a polymer composed of two types of saccharides, galactose and arabinoz, in a ratio of 6:1 respectively.

Methods for the extraction of arabinogalactane have been described, in particular from coffee (EP 1 600 461, WO 2007/099997) and from lettuce (EP 0 866 808).

Arabinogalactan has many effects on mammalian metabolism, including the following: Arabinogalactans are non-digestible fibres with a prebiotic action, i.e. which promote the proliferation of beneficial bacteria in the digestive tract.Arabinogalactan has a reputation for boosting the immune system.Application EP 1 600 461 specifically claims that arabinogalactan should be added to foods to obtain healthy foods.Arabinogalactan stimulates the secretion of interleukin-12 which promotes DNA repair (FR2836378).Application WO 2010/020379 describes the following compounds containing arabinogalactan for the prevention and treatment of allergic and inflammatory diseases: arabinogalactan has significantly reduced acute effects.Application WO 2010/0235 describes arabinogalactan as a protective agent for the prevention of acute inflammatory diseases. It promotes cell renewal, particularly of fibroblasts; it stimulates the expression of collagen types I and III; it inhibits the secretion of IL-1β.

Surprisingly, the authors of the present application have demonstrated another beneficial effect of arabinogalactan on the treatment and prevention of skin redness: it has interesting properties in limiting the proliferation of endothelial cells during episodes of skin redness, and its anti-redness action is further enhanced when used in combination with lupin peptides.

The invention is described in detail in the following table:

The present invention relates to a method of preventing and/or treating skin redness, including administration of a composition containing arabinogalactane, to a person who is susceptible to or has redness.

The composition may also include other anti-redness compounds, such as lupin peptides, which have synergistic effects on the various molecular phenomena involved in the appearance of redness.

The manufacturer shall provide the manufacturer with a detailed description of the device.

Due to its regulatory properties of innate immunity and neoangiogenesis, arabinogalactan can reduce the reactivity of certain skin types susceptible to developing redness, and thus prevent and treat the appearance of redness.

'Redness of the skin' refers to facial erythema and telangiectasia of all origins.

The expression prevention of skin redness is used to describe an action to prevent or at least reduce the formation of unsightly redness by application of the composition before and during an event known to cause redness, such as sun exposure or stress.

The expression treatment of skin redness means, according to the present invention, an action to reduce unsightly symptoms by application of the composition on the redness.

The expression composition containing arabinogalactane is intended to indicate that the compound "arabinogalactane" is the active substance of the composition, i.e. that it has an action of its own as such on the prevention and treatment of skin redness. As shown in the examples, arabinogalactane acts on different molecular factors involved in the appearance of redness: inhibition of LL37 expression, inhibition of endothelial cell proliferation and inhibition of VEGF expression.

a person who is likely to develop or has redness means a person who considers redness on the face to be unsightly and disabling, regardless of the stage at which such redness can be classified from a clinical point of view.

According to a preferred aspect of the invention, the above composition is administered topically, particularly to areas of skin that may become red, including the face.

The composition may also be administered orally, in particular as tablets, capsules, soft capsules, dressing, emulsions, gels, or as supplements or food products.

According to a preferred aspect of the invention, the arabinogallactan used is extracted from lettuce. A process of extraction is described in particular in patent application EP 0 866 808. According to a preferred aspect of the invention, the lettuce from which the arabinogallactan is derived is grown in a reasonable and sustainable manner. Arabinogallactan can also be extracted from herbs, including prairie foxglove, prairie fleabane, dactyl or rye.

Preferably, the anti-redness composition of the invention includes arabinogalactane in a proportion of between 0,01% and 10% by weight, preferably between 1 and 5%, and more preferably in a proportion of about 2% by weight to the total weight of the composition.

Depending on a preferred aspect of the invention, the anti-redness composition includes at least one other anti-redness agent, selected in particular from the following list: lupin peptides, permethol, genistein, esculoside, dextran sulphate, methylchalcone hesperidin, retinoids, lycochalcone, oxymethazoline, kinetin, licorice extract, vitamin P like, holly extract, Sophora japonica, hamamelis extract, ruscus, antibiotics such as doxycycline, polyphenols including tanins, phenolic acids, anthocyanins, procyanidins, phenylalanine with e.g. the redness of tea, citrus fruits, citrus root extracts, citrus, citrus fruits, citrus fruits, citrus fruits.

Each of these compounds has its own action to amplify or promote the action of arabinogalactan on redness of the skin.

According to a preferred aspect of the invention, the composition includes arabinogalactane and lupin peptides.

Lupin peptides means any preparation containing a peptide-enriched lupin extract, such as, for example, the following preparations: the protein hydrolysates Structurine® and Anagelin®, marketed by Silab; the peptide hydrolysate of lupine 'Sweet Blue Lupine Peptides®', marketed by Oat Cosmetics.

A preferred preparation of lupin peptides is the preparation marketed by the company Laboratori Expanscience, obtained by the process described in application WO2005/102259.

In particular, the composition according to the invention includes between 0,01% and 10% arabinogalactane, and between 0,01% and 10% lupin peptides.

A preferred composition includes 2% arabinogalactane and 0.2% lupin peptides.

According to a preferred aspect of the invention, the anti-redness composition also includes at least one soothing and restructuring agent, selected in particular from the following agents: a peptide extract of quinoa or oxazoline, a concentrate of sunflower oil, a vitamin E acetate and various mixtures of these compounds.

Each of these compounds has its own action to amplify, supplement or promote the action of arabinogalactane and optionally lupin peptides on red skin.

Quinoa peptide extract means in particular an extract from quinoa seeds as described in international application WO2008/080974, which is characterised by having between 10 and 90% by weight of peptides and between 10 and 50% by weight of sugars in relation to the total weight of the extract and is used for its barrier-repairing and anti-inflammatory properties.

The sunflower oil concentrates that may be used in the present invention in combination with arabinogalactane are advantageously linoleic sunflower concentrates, such as the active substance marketed by Expanscience Laboratories, Soline® (see International Application WO 01/21150), particularly for their restructuring and anti-irritant and/or soothing activity.

The oxazolins that may be used in combination with arabinogalactane are oxazolins that are advantageously selected from the group consisting of 2-undecylen-4-hydroxymethyl-4-methyl-1,3-oxazoline, 2-undecylen-4,4-dimethyl-1,3-oxazoline, (E)-4,4-dimethyl-2-heptadec-8-enyle-1,3-oxazoline, 4-hydroxymethyl-4-methyl-2-heptadecyl-1,3-oxazoline, (E)-4-hydroxymethyl-4-methyl-2-heptadecyl-8-amethyl-1,3-oxazoline, 2-undecylen-4-hydroxymethyl-1,3-oxazoline, (E)-4,4-dimethyl-1,3-dimethyl-1,3-oxazoline, (E)-4,4-hydroxymethyl-4-methyl-1,3-oxazoline, (D)-1,4-dimethyl-1,3-oxazoline, (D)-1,4-dimethyl-1,3-oxazoline, or WOX-12, and WOX-12, and WOX-12, and WOX-1200, and/or 2-methyl-1,3-dimethyl-1, or WOX-1, are particularly useful for their anti-inflammatode activity.

The composition according to the invention may further include at least one compound chosen from the group consisting of moisturizing and/or healing and/or restructuring agents and/or anti-irritant and/or soothing and/or anti-oxidant and/or anti-aging agents.

The active moisturizers/softeners may be glycerin or its derivatives, urea, pyrrolidone carboxylic acid and its derivatives, hyaluronic acid of any molecular weight, glycosaminoglycans and any other polysaccharides of marine, plant or biotechnological origin such as xanthan gum, fucogel®, fatty acids such as lauric acid, myuric acid, poly- and monounsaturated fatty acids of omega 3, 6 and 7, 9 such as linoleic acid and palmitic acid, some butter such as shea butter.

Healing and/or skin barrier repair agents that can be used in combination are panthenol (vitamin B5), zinc oxide, madacassic or asiatic acid, dextran sulfate, coenzyme Q10, glucosamine and its derivatives, chondroitin sulfate and globally glucosaminoglycans, dextran sulfate, ceramides, cholesterol, squalene, phospholipids. PPAR agonists (rosiglitazone, pioglitazone), RXR, LXR may also be used.

Anti-inflammatory and/or anti-irritant and/or soothing agents may be glycyrrhetic acid (the derivatives of licorice) with its salts and esters, lipoic acid, beta-carotene, vitamin B3 (niacinamide, nicotinamide), vitamin E, vitamin C, vitamin B12, lycopene or lutein, spring or thermal waters (water of Avena, water of the Posay Rock, water of St Gervais, water of Uriage, Gamarde water), or topical disulfone, or steroidal anti-inflammatory drugs (SIA), such as soy corticosteroids, non-steroidal steroids (SIN).

Antioxidants that can be used in combination are advantageously chosen from the group consisting of thiols and phenols, by licorice derivatives such as glycyrrhetinic acid with its salts and esters, alpha bisabolol, lipoic acid, vitamin B12, vitamin B3 (niacinamide, nicotinamide), vitamins C, vitamins E, coenzyme Q10, krill, glutathione, BHT for butylhydroxytoluene, BHA for butylhydroxyan, lycopene or lutein, beta-carotene. In the group of antioxidants, we also find anti-glycation substances such as peroxide, n-acetyl or n-acetyl carotene, as well as certain antioxidants such as agnostic acid, peroxide, peroxide, or their antagonists, such as agnostic acid, agnostic acid, or their antagonists, such as catacalysts, acetobacterase and agnostic acid.

Anti-aging agents may include vitamin C, hyaluronic acid of any molecular weight, retinoids such as retinol, retinal and retinoids; in particular, non-aromatic retinoids such as retinaldehyde, tretinoin, isotretinoin and 9-cis retinoic acid, vitamin A, monoaromatic retinoids such as etretinate, all-transfone acitretin and motrerinide, and polyaromatic retinoids such as adapalene, tazarotene, tamibarotene and arotinoid methyl sulphate.

In addition, the composition according to the invention may also include mineral or organic (pigmented or ultrafine) filters and sunscreens, antifungal compounds, preservatives and antibacterial agents.

Examples of sunscreen products which can be used in combination are UVB and/or UVA sunscreens and/or filters, such as mineral and/or organic sunscreens and/or filters which are known to the professional and which will be selected and concentrated according to the degree of protection sought. Examples of sunscreen include titanium dioxide, zinc oxide, methylene bis-benzotriazolyltramethylbutylphenol (commercial name: TINOSORB M) and Bis-ethylxyphenolhoxyphenol triazine (commercial name: TINOSORB S), electrolytic acid, butylmethylmethylmethylmethylhexide, terephthalic acid, dicylmethylmethyl sulphate, 4-methylmethylmethylmethyl butyl, dimethylmethylmethyl butyl, butylmethylmethylmethyl PABA, dimethylmethylmethylmethyl, butylmethylmethylmethylmethyl.

Antifungal compounds that can be used in combination are econazole and ketoconazole.

Preservatives that can be used in combination include, for example, those commonly used in cosmetics or nutraceuticals, antibacterial molecules (pseudo-preservatives) such as caprylic derivatives such as capryloyl glycine and glyceryl caprylate, such as hexanediol, and sodium levulinate, zinc and copper derivatives (gluconate and PCA), phytosphingosine and its derivatives, benzoyl peroxide, pyridoxine olamine, zinc pyrithione, selenium sulfide.

Antibiotics that can be used in combination are fucidic acid, penicillin, tetracyclines, pristinamycin, erythromycin, clindamycin, mupirocin, minocycline, doxycycline, and antiviral agents that can be used in combination are acyclovir and valacyclovir.

The active substances recommended in combination with the extract of the invention include plant extracts, in particular: Vegetable oils such as soybean and/or rapeseed oils, avocado oil (WO2004/012496, WO2004/012752, WO2004/016106, WO2007/057439), lupine oil, preferably sweet white lupine oil (WO 98/47479), squash seed oil (sebo-regulator), melaleuca oil (anti-dandruff), borage oil (anti-dandruff), cod liver oil; distillate or concentrates of vegetable or animal oil, sunflower oil, more preferably linoleum concentrates, such as actin marketed by Laboratories Solanscience, (cf. Avocatine® 011/50), the international demand formaize or palm oil, useful in particular for their moisturising and/or emollient, healing and/or skin-barrier-restructuring, anti-inflammatory and/or anti-irritant and/or soothing properties; vegetable or vegetable oil unsaponifiables, preferably avocadofurane® (avocado furanes, which can be obtained by the process described in international application WO1/21605), avocado and soybean unsaponifiables, in particular a mixture of avocado unsaponifiables and soybean unsaponifiables, in a ratio of approximately 1/3-2/3 (such as soybean PiDel®), avocado unsaponifiables (which can be obtained by the process described in international application WO1/21605), avocado and soybean unsaponifiables, in particular a mixture of avocado unsaponifiables and soybean unsaponifiables, which is obtained by the international application WO1596/51 (which is between 20% and 95% alcohol, and 95% alcohol, which is obtained by the use of soybean unsaponifiable in the process WO155 and 95% alcohol, which is obtained by the use of soybean unsaponifiable in the process WO15/51 and the international application WO155/51 (which is obtained by the use of the use of the use of the method WO156 and the use of the method WO156 and the use of the method WO155),preferably 45 to 65% by weight of the total weight of the unsaponifiable), phytosterols, sterol esters and vitamin derivatives, useful in particular for their healing and/or skin barrier restructuring activity, anti-aging, anti-inflammatory peptides or plant amino acid complexes, in particular avocado peptides (as described in international application WO2005/105123), lupin peptides (as obtained by the process described in international application WO2005/102259), quinoa peptides (as described in international application WO2008/080974), soya peptides such as those described in international application WO2004/112742), or maca peptides,rice peptides (as described in international application WO 2008/009709), useful in particular for their moisturising and/or emollient (avocado), keratoglycerin (lupin, quinoa), healing and/or skin barrier repair (maca, quinoa, soybean), anti-inflammatory and/or anti-irritant and/or soothing (lupin, quinoa, schizandra), antioxidant (avocado), anti-aging (sisropin, maca, avocado), pigment (riz) and vegetable juices, in particular avocado sugars (as described in application WO 2005/115421), useful in particular for their barrier repair, scarring and/or skin repair (maca, quinoa, soybean), anti-inflammatory and/or anti-irritant and/or soothing (lupin, quinoa, schizandra), antioxidant (avocado), anti-aging (sisropin, maca, avocado); inhibits the secretion of vegetable juices, in particular avocado sugars (as described in application WO 050515421/1), useful in particular for their scarring, scarring and/or repair and/orritriting action (avocado); in the case of avocado, anti-inflammatory and/or, anti-inflammatory and/or (avocado-authorizing) in the extract of the extract of pheny (FR 0521 021 021 05); in the case of 1 (FR 0521 021 02); in the case of 1 FR 5 (FR 021 021 02); in the case of 1 FR 021 021 021 021 021 (FR 021 02); in the extract of pheny (FR1 5 (FR1 021 02); in the extract of pheny (FR1 5/281 5281 5/FR1 5 (FR1 52) and 1 FR1 5 (FR1 02); in the extract of pheny (FR1 5 (FR1 5/251 52); in the extract of pheny) 1 (FR1 5 (FR1 5 (FR1 52); in the extract of pheny) 1 (FR1 5 (FR 2 857 596) is particularly useful for promoting healing,a total lupin extract (such as those described in international application WO2005/102259), particularly suitable for the treatment of irritations;isoflavones such as soy isoflavones;a cupuaçu butter, particularly appreciated for its moisturising properties;a peptide and oxide extract of Acacia macrostachya seeds (FR 0958525), adapted for its moisturising properties;an extract of Vigna unguiculata seeds (FR 08529);an extract of Schizandra sphenanthera fruit (such as those described in applications FR 0955344, 2011/012612) and a peptide extract of Schizandra (FR 0955343 and WO 2011/0615) adapted for its anti-inflammatory and anti-inflammatory properties.

The topical composition of the invention also includes a suitable vehicle which may be any vehicle among those known to the trade in order to obtain a cosmetic composition usable according to the invention, in particular in the form of a cream, lotion, gel, spray, patch, water, ointment, milk or oil, possibly in the form of an emulsion, with addition of components known to the trade to improve, modify or stabilize the composition from a cosmetic point of view.

In particular, arabinogalactan and the other active substances of the invention can be incorporated into all forms of food supplements or fortified foods, for example, food bars, compacted or uncompacted powders, beverages, dairy products and especially yogurts and yogurts for drinking. The powders can be diluted in water, sodas, fruit juices, dairy or soy products, rice, or incorporated into food bars.

The operating conditions for preparing these compositions according to the invention are part of the general knowledge of the professional.

The present invention also relates to the use of arabinogalactane to prevent and/or treat the appearance of redness on the skin.

The present invention also relates to the use of a combination of arabinogalactane and lupin peptides to prevent and/or treat the appearance of redness on the skin.

The present invention also relates to a therapeutic composition containing arabinogalactane for use in the prevention and/or treatment of skin rashes.

The invention also relates to a method of prevention and/or treatment of skin redness, including topical or oral administration of a composition containing arabinogalactane.

The present invention also relates to a composition containing arabinogalactane and lupin peptides for use in the prevention and/or treatment of skin redness.

The invention also relates to a method of prevention and/or treatment of skin redness, including topical or oral administration of a composition containing arabinogalactane and lupin peptides.

The present invention also relates to a composition containing arabinogalactane for use in the prevention and/or treatment of rosacea.

Redness may be associated with the early stages of rosacea, a mild chronic skin condition that mainly affects the face and is characterised by flushing, permanent erythema, papules, pustules and telangctasis. Stage I: erythematotellectasis rosacea: flush, persistent erythema and telangectasis; Stage II: papulopustular rosacea or rosacea: persistent erythema, papules and pustules; Stage III: phymas or phymatous rosacea; Stage IV: ocular rosacea.

The invention also relates to a method of prevention and/or treatment of rosacea, including topical or oral administration of a composition containing arabinogalactane.

The present invention also relates to a composition containing arabinogalactane and lupin peptides for use in the prevention and/or treatment of rosacea.

The invention also relates to a method of prevention and/or treatment of rosacea, including topical or oral administration of a composition containing arabinogalactane and lupin peptides.

The figures

Figure 1: Key role of innate immunity in the occurrence of redness in people prone to redness, compared to normal skin; Reviewed by Bevins CL and Liu FT [7]Figure 2: Synergy of effects of the combination of arabinogalactane and lupin peptides on LL37 and VEGF expression.

Examples

In vitro samples, the active substances are diluted to 0.2% for arabinogalactane and 0.02% for lupin peptides; in the final cosmetic formulations, the concentrations used will be ten times higher (2% arabinogalactane, 0.2% lupin).

1. Effects of arabinogalactane and the combination of arabinogalactane and lupin peptides on gene expression of kallikrein 5 (KLK5) and cathelicidin (LL37)

To evaluate the potential activity of arabinogalactane, possibly in combination with lupin peptides, in the inflammatory phase of skin redness, we investigated the effect of this complex of active substances on the expression of the cathelicidin LL37 and kallikrein 5 (KLK5) induced by a vitamin D analogue (calcitriol) in keratinocytes.

Equipment and methods

Normal human epidermal keratinocytes (NHEK) were cultured in a Ca++ supplemented differentiated culture medium.

Keratinocytes were treated for 24 hours with the active substances arabinogalactane (ARG) / lupin peptides (LUP) at concentrations of 0.2% / 0.02% alone or in combination with or without calcitriol (vitamin D analogue).

At the end of the treatment, the culture surfactants were removed and the total RNAs were extracted, analysed and dosed.The newly synthesised cDNAs for the genes of interest (LL37 and KLK5) or reference genes were selectively amplified by real-time PCR on iQ5 [Biorad] by SybrGreen technology.

For each sample, the expression level of the gene of interest was normalized by the expression level of the most stable reference gene (GAPDH gene). From the calculations of ΔCt (Ctgene of interest - Ctgene of reference) and ΔΔCt (ΔCtcontrol - ΔCttraity), the relative amount of the gene of interest was measured: QR = (1+E) ΔΔCt, assuming that E (efficiency) is equal to 1, so we have QR = 2ΔΔCt.

The significance of the results was verified on ΔCt values by a one-factor variance analysis followed by a Tuckey test.

The inhibition percentage of LL37 and KLK5 expression is calculated as follows:

Results Gene expression of LL37 (Table 1 and Figure 2):

Calcitriol strongly and significantly stimulated the expression of LL37 by keratinocytes (+812%, p< 0.001).

Arabinogalactane used at 0.2% significantly inhibits LL37 expression by 18%.

The combination of active substances arabinogalactan + lupin peptides inhibits the LL37 gene expression induced by calcitriol by 53% due to the synergistic effect of the combination of arabinogalactan and lupin peptides, which inhibits LL37 expression more moderately when tested alone.

		Ecart type	ΔΔCt
Cellules contrôles	14,21	0,69		1,00
Témoin stimulé (Calcitriol)	11,02	0,28	3,19	9,12 $$$
ARG 0,2%	11,31	0,57	2,9	7,46*	18,2%
PLU 0,02%	11,14	0,66	3,07	8,39 ns	7,9%
ARG 0,2% +PLU 0,02%	12,12	1,10	2,09	4,25**	53,3%

The following is the list of active substances in the active substance:

Calcitriol strongly and significantly stimulated the expression of kallikrein 5 by keratinocytes (+149%, p< 0.001).

The combination of active substances arabinogalactane + lupin peptides significantly inhibited the gene expression of KLK5 induced by calcitriol (39% inhibition). - What?

		Ecart type	ΔΔCt
Cellules contrôles	3,78	0,99	0	1,00
Témoin stimulé (Calcitriol)	2,46	1,35	1,32	2,49 $$$
ARG 0,2% +PLU 0,02%	3,18	1,25	0,6	1,52	39,3%

The Commission

In these experimental conditions, the combination of active substances arabinogalactane + lupin peptides allowed synergistic modulation of the expression of cathelicidin LL37 and the enzyme responsible for its maturation, kallikrein 5.

Thus, the combination of arabinogalactane/ lupine peptides helps to modulate the induction of the TLR2/KLK5/LL37 pathway-dependent immune and inflammatory response in the onset of skin redness.

Activity on vascular parameters: proliferation of endothelial cells Equipment and methods

Normal human dermal micro-vascular endothelial cells were incubated for 24 or 48 hours in the absence (control) or presence of the active substances arabinogalactan (ARG) / lupin peptides (LUP) at concentrations of 0.2% / 0.02% alone or in combination with and in the presence of the reference activator VEGF (Vascular Endothelial Growth Factor).

At the end of incubation, the viability of the cells was assessed by a spectrophotometric method: p-nitrophenyl phosphate (PNPP) is converted to p-nitrophenol by phosphatases in viable cells and the absorbance at 405 nm of p-nitrophenol is directly proportional to the number of viable cells.

The results shall be expressed as a percentage of the signal PNPP of the control without VEGF at T0 (mean ± standard deviation).

The statistical significance of the differences between the conditions cell stimulated VEGF and VEGF+ active was assessed by a one-factor variance analysis followed by a Holm-Sidak test.

The percentage of inhibition of proliferation is calculated by the following equation:

Results 2.1 Endothelial cell proliferation in the presence of VEGF (Table 3):

VEGF, an angiogenic factor, stimulates the growth of endothelial cells compared to control cells (not treated with VEGF): +78.9% (p<0.01) after 24 hours of incubation and +159% (p<0.01) after 48 hours of incubation.

In the presence of arabinogalactane, this growth stimulation is reduced by 17% at 24 hours and by almost 10% at 48 hours.

In the presence of the combination of arabinogalactane + lupin peptides, VEGF-induced endothelial cell proliferation is significantly inhibited (50% and 25% inhibition at 24 and 48 h respectively), with synergistic action of the two agents.

Cellules contrôle sans VEGF	163,3 ± 8		162,8 ± 8,3
Témoins stimulés VEGF	213,2 ± 10,8		262,6 ± 5
ARG 0,2%	204, 7 ± 7,1	17,03%	252,9 ± 6	9,71%
PLU 0,02%	209,1 ± 6,4	8,22%	259,3 ± 7,2	3,31%
ARG 0,2% + PLU 0,02%	187,8 ± 4,1	50,90% p<0,05	237,2 ± 9,9	25,45% p<0,05

Arbinogalactan, by limiting the proliferation of endothelial cells, helps to limit the early phase of angiogenesis.

The combination of arabinogalactan + lupin peptides is more effective than arabinogalactan alone in limiting this cell proliferation.

The following are the main characteristics of the gene expression of angiogenesis markers: VEGF, FGF2, HIF1α, thrombospondin

In order to understand the antiangiogenic effect of arabinogalactane, the keratinocyte gene expression of certain markers involved in angiogenesis was studied. VEGF and FGF2 expression, proangiogenic growth factors: VEGF (Vascular endothelial growth factor) is the major growth factor of vascular endothelium. It is a potent vasoactive and inflammatory cytokine that acts directly on endothelial cells by stimulating their migration and proliferation and thus promotes neoangiogenesis. Furthermore, VEGF leads to an increase in the permeability of endothelial cells whose plasma proteins will spill into the vascular matrix (vascular recto-extractability). VEGF has chemotoxic properties that allow the inflammatory cells to leak. VEGF is secreted by mastocytes, red blood cells, keratocytes, and reticulocytes, and its receptors are present in VEGF cells and inflammatory cells.[12] FGF2 or bFGF: growth factor synthesised by keratinocytes, fibroblasts, inflammatory cells and endothelial cells and a potent regulator of angiogenesis in synergy with VEGF. HIF1α, a transcription factor for VEGF, and thrombospondin, an antiangiogenic factor.

Equipment and methods

Normal human epidermal keratinocytes (NHEK) were incubated in the presence of the active compound arabinogalactan (ARG) / lupin peptides (LUP) at concentrations of 0.2% / 0.02% alone or in combination.

At the end of the treatment, the culture surfactants were removed and the total RNAs were extracted, analysed and dosed.The newly synthesised cDNAs related to the genes of interest (VEGF, FGF2, HIF1α, THBS1) or the reference genes were selectively amplified by real-time PCR on iQ5 [Biorad] by SybrGreen technology.

For each sample, the expression level of the gene of interest was normalized by the expression level of the most stable reference gene (GAPDH gene). From the calculations of ΔCt (Ctgene of interest - Ctgene of reference) and ΔΔCt (ΔCtcontrol - ΔCttraity), the relative amount of the gene of interest was measured: QR = (1+E) ΔΔCt, assuming that E (efficiency) is equal to 1, so we have QR = 2ΔΔCt.

The significance of the results was verified on ΔCt values by a one-factor variance analysis followed by a Dunnett test.

The % inhibition is calculated for VEGF, FGF2 and HIF 1α:

The stimulation percentage is calculated for THBS 1:

Results 2.2.1 Gene expression of the VEGF (Table 4 and Figure 2)

Arabinogalactan significantly inhibits VEGF expression by 29%.

The combination of active substances arabinogalactan/ lupin peptides very strongly and significantly inhibited keratinocyte VEGF expression (86% inhibition) and much more than the active substances tested alone.

		Ecart type	ΔΔCT
Cellules contrôles	8,53	0,58		1
ARG 0,2%	9,03	0,62	-0,5	0,707**	29,3%
PLU 0,02%	8,7	0,98	-0,17	0,889 ns	11,1%
ARG 0,2% + PLU 0,02%	11,44	1,34	-2,91	0,133 ***	86,7%

2.2.2. gene expression of FGF2 (Table 5):

The combination of active substances arabinogalactane/ lupin peptides completely and significantly inhibited keratinocyte expression of FGF2. - What?

		Ecart type	ΔΔCT
Cellules contrôles	6,97	0,83		1	1
ARG 0,2% + PLU 0,02%	14,34	1,37	-7,37	0,006 ***	99,4%

The following is a list of the genes expressed by HIF1α (Table 6):

The combination of active substances arabinogalactane/ lupin peptides significantly inhibited the expression of the transcription factor HIF1α by keratinocytes (54% inhibition).

		Ecart type	ΔΔCT
Cellules contrôles	5,5	1,3		1
ARG 0,2% + PLU 0,02%	6,63	1,22	-1,13	0,456 **	54,3%

The following are the main characteristics of the blood plasma:

The combination of active substances arabinogalactane/ lupine peptides significantly stimulated the expression of antiangiogenic factor thrombospondin by keratinocytes (76% increase). - What?

		Ecart type	ΔΔCT
Cellules contrôles	4,34	1,8	0	1
ARG 0,2% + PLU 0,02%	3,52	1,44	0,82	1,765 *	76,5%

The Commission

In the experimental conditions presented above, we were able to show that the combination of arabinogalactane/lupin peptides modulates the expression of factors involved in angiogenesis induction, in favour of an antiangiogenic effect, as the active substance was able to decrease the expression of proangiogenic markers (FGF2, VEGF) and increase the expression of an antiangiogenic marker (THBS1). In addition, an inhibitory effect was also observed on the VEGF transcription factor (HIF1-α), suggesting regulation by the upstream active substance of VEGF via its transcription factor.

Thus, by inhibiting angiogenesis, an early phenomenon of neovascularisation, the combination of arabinogalactane and lupin peptides helps to limit the activation of endothelial cells and the synthesis of new blood vessels.

Gene expression of MMP-2 and -9, markers of neovascularization

The effect of the combination of active substances arabinogalactane/ lupin peptides has been investigated on genes involved in molecular phenomena of neovascularization.

Thus, the gene expression of two Matrix metalloproteinases was studied: MMP-2 and MMP-9, which are responsible for the degradation of the extracellular matrix and promote the migration of endothelial cells, a step in angiogenesis, which is necessary for the formation of new blood vessels.

The effect of the active substances was investigated at baseline (for MMP2) or as a preventive measure in cell mates that had undergone inflammatory stress induced by PMA (for MMP9).

Equipment and methods

Normal human epidermal keratinocytes (NHEK) were pre-incubated for 24 h in the presence of active arabinogalactan (ARG) / lupin peptides (LUP) at concentrations of 0.2% / 0.02%. PMA was then added for a total treatment time of 40 h. For baseline evaluation, the cells were simply incubated for 40 h in the presence of active arabinogalactan (ARG) / lupin peptides (LUP) at concentrations of 0.2% / 0.02%.

At the end of the treatment, the culture surfactants were removed and the total RNAs were extracted, analysed and dosed.The newly synthesised cDNAs for the genes of interest (MMP2, MMP9) or reference genes were selectively amplified by real-time PCR on iQ5 [Biorad] by SybrGreen technology.

For each sample, the expression level of the gene of interest was normalized by the expression level of the most stable reference gene (GAPDH gene). From the calculations of ΔCt (Ctgene of interest - Ctgene of reference) and ΔΔCt (ΔCtcontrol - ΔCtraity), the relative amount of the gene of interest was measured: QR = (1+E) ΔΔCt, given that E (efficiency) is equal to 1, so we have QR = 2ΔΔCt.

Significance of the results was verified on ΔCt values by a one-factor variance analysis followed by a Dunnett (for MMP2) or Tuckey (for MMP9) test.

The % inhibition is calculated for MMP2 as follows:

The % inhibition is calculated for MMP9 as follows:

Results The following is a list of the most commonly used MMP2 gene expression methods:

The combination of active substances arabinogalactane/ lupin peptides significantly inhibited MMP2 gene expression (23% inhibition). - What?

		Ecart type	ΔΔCT
Cellules contrôles	6,99	0,72		1	1
ARG 0,2% + PLU 0,02%	7,38	0,98	-0,39	0,76 *	23,7%

The following is a list of the most commonly used MMP9 genes:

PMA significantly and very strongly stimulated MMP9 expression in keratinocytes, and under these conditions the combination of active substances arabinogalactan and lupin peptides inhibited PMA-induced MMP9 expression (54% inhibition).

		Ecart type	ΔΔCT	Expression de MMP9 Quantité relative	% Inhibition
Cellules contrôles	8,87	1,16		1
Témoin stimulé (PMA)	2,32	1,03	6,55	93,70 $$$
ARG 0,2% + PLU 0,02%	3,46	0,7	5,41	42,51 *	54,6%

The Commission

Under the experimental conditions described above, an inhibitory effect of the expression of the MMP2 and MMP9 matrix proteases was shown for the arabinogalactane/ lupin peptides combination.

Thus, by reducing the degradation of extracellular matrix, the active substances help to limit the influx of endothelial cells, an early stage of neovascularization.

Activity on an inflammatory parameter: IL8 Equipment and methods

Human keratinocytes (NCTC 2544) were pre-incubated for 24 hours with the active substances arabinogalactane (ARG) / lupin peptides (LUP) at concentrations of 0.2% / 0.02%; or with the reference molecule dexamethasone.

Inflammation was then induced by treatment with PMA for 24 hours, always in the presence of the active substance or reference molecule.

At the end of incubation, the amounts of interleukin-8 (IL8) present in the culture surrogates were measured by ELISA.

The significance of the results was verified by a one-factor analysis of variance followed by a Tuckey test.

The inhibition percentage is calculated using the following formula:

The results (Table 10)

Treatment with PMA significantly stimulated the release of IL8 by keratinocytes, dexamethasone significantly inhibited this release (-81%), these results validate the trial. - What?

Cellules contrôles	0,1033 +/- 0,002
Témoin stimulé (PMA)	30,60 +/- 1,888	$$$
5,967 +/- 0,203	80,5% ***
ARG 0,2% + PLU 0,02%	20,40 +/- 1,559	33,3% **

The Commission

In these experimental conditions, the combination of active substances arabinogalactane + lupin peptides showed a modulatory effect on the inflammatory mediator IL8.

The Commission therefore concludes that the aid was necessary.

The following effects are reported with arabinogalactan: In addition, the effects of the drug on the liver and kidney are also important, as shown by the following:

This makes it a good active ingredient for the prevention and/or treatment of redness.

The combination of this active substance with lupin peptides provides much better results, by acting on most of the factors involved in skin redness such as immune and inflammatory factors and vascular and dermal factors.

4. Examples of compositions for topical application

The inventors present several compositions for topical application below. Arabinogalactane and lupine peptides can be incorporated into various cosmetic products such as cleaning waters, emulsions, creams, milks, lotions, foaming products and sprays, the compositions of which are presented below.

The following shall be added to the list of substances:

AQUA (WATER)	QSP 100%
GLYCERIN	De 1 à 15 %
DICAPRYLYL CARBONATE	De 1 à 10 %
DICAPRYLYL ETHER	De 1 à 10 %
CAPRYLIC/CAPRIC TRIGLYCERIDE	De 1 à 10%
GLYCERYLSTEARATE	De 1 à 5%
FILTRES SOLAIRES CHIMIQUES	De 1 à 10%
BUTYROSPERMUM PARKII (SHEA) BUTTER	De 1 à 5%
CETYL ALCOHOL	De 1 à 5%
DEXTRIN PALMITATE	De 0 à 2%
LAURETH-23	De 0 à 2%
HYDROXYETHYL ACRYLATE/SODIUM ACRYLOYLDIMETHYL TAURATE COPOLYMER	De 0 à 2%
PEG-75 STEARATE	De 0 à 2%
CERA ALBA (BEESWAX)	De 0 à 2%
CONSERVATEURS	De 0 à 2%
CETETH-20	De 0 à 0.5%
STEARETH-20	De 0 à 0.5%
DECYL GLUCOSIDE	De 0 à 0.5%
XANTHAN GUM	De 0 à 0.5%
TOCOPHERYL ACETATE	De 0 à 0.5%
CETEARYL ALCOHOL	De 0 à 0.5%
CETYL PALMITATE	De 0 à 0.5%
COCOGLYCERIDES	De 0 à 0.5%
EXTRAIT PEPTIDIQUE DE QUINOA	De 0,01 à 10 %
CYCLOCERAMIDES	De 0,01 à 10 %
	De 0,01 à 10%
CONCENTRAT D'HUILE DE TOURNESOL	De 0,01 à 10 %
COLORANT	De 0 à 0.5%
CITRIC ACID	De 0 à 0.5%

The following shall be added to the list of substances:

AQUA (WATER)	QSP 100%
GLYCERIN	De 1 à 15 %
PROPANEDIOL DICAPRYLATE	De 1 à 15 %
DICAPRYLYL CARBONATE	De 1 à 15 %
GLYCERYLSTEARATE CITRATE	De 1 à 5%
CONSERVATEURS	De 1 à 5%
CETYL ALCOHOL	De 1 à 5%
ACRYLATES/C10-30 ALKYL ACRYLATE CROSSPOLYMER	De 0 à 2%
GLYCERYL CAPRYLATE	De 0 à 2%
SODIUM STEAROYL GLUTAMATE	De 0 à 2%
TOCOPHERYL ACETATE	De 0 à 2%
SODIUM HYDROXIDE	De 0 à 2%
EXTRAIT PEPTIDIQUE DE QUINOA	De 0,01 à 10 %
CYCLOCERAMIDES	De 0,01 à 10 %
PEPTIDES DE LUPIN	De 0,01 à 10 %
	De 0,01 à 10 %
CONCENTRAT D'HUILE DE TOURNESOL	De 0,01 à 10%
BISABOLOL	De 0 à 2%

Clean water is not sensitive

CAPRYLOYL GLYCINE	De 0 à 1 %
LESSIVE SOUDE	De 0 à 1 %
SEQUESTRANT	De 0 à 1 %
BUTYLENE GLYCOL	De 1 à 5 %
BETA CAROTENE	De 0 à 2 %
CYCLOCERAMIDES	De 0,01 à 10 %
De 0,01 à 10 %
CONSERVATEURS	De 0 à 1 %
PEG-32	De 1 à 5 %
PEG-7 PALMCOCOATE	De 1 à 5 %
GLUCONATE ZINC	De 0 à 1 %
ACIDE CITRIQUE	De 0 à 1 %
EAU PURIFIÉE	QSP 100 %
PARFUM	De 0 à 1%
POLOXAMER 184	De 1 à 5 %

The following shall be added:

ISOPARAFFINE LIQUIDE	De 5 à 20 %
STEARATE D'ISOCETYLE	De 5 à 20 %
HYDROXYSTEARATE AL - MG	De 5 à 20 %
ABIL WE 09	De 1 à 5 %
GLYCEROL	De 1 à 5 %
HUILE VASELINE	De 1 à 5 %
ZINC OXYDE MICRONISE	De 1 à 5 %
BUTYLENE GLYCOL	De 1 à 5 %
RETINOL	De 0 à 1%
VITAMINE C	De 0 à 5%
De 0,01 à 10 %
PEPTIDES DE LUPIN	De 0,01 à 10 %
PEPTIDES DE MACA	De 0,01 à 10 %
ISONONYL ISONONANOAT	De 1 à 5 %
CIRE D'ABEILLE	De 1 à 5 %
TARTRATE DE SODIUM	De 1 à 5 %
CHLORURE DE SODIUM	De 0 à 5 %
GLYCINE	De 1 à 5 %
CONSERVATEURS	De 0 à 1 %
CHOLESTEROL	De 0 à 1 %
PHYTOSPHINGOSINE	De 0 à 1 %
ACIDE TARTRIQUE	De 0 à 1 %
EAU PURIFIÉE	QSP 100 %

The following shall be added to the list of substances:

HYDROGENATED POLYDECENE	De 5 à 20%
LAURYLGLUCOSIDE-GLYSTEARATE	De 1 à 5%
DICAPRYLYL CARBONATE	De 1 à 5 %
GLYCEROL	De 5 à 20%
CARBOPOL	De 0 à 1%
GOMME XANTHANE	De 0 à 1 %
ACIDE ASIATIQUE	De 0 à 1 %
VITAMINE B5	De 0 à 5 %
	De 0,01 à 10 %
EXTRAIT PEPTIDIQUE DE QUINOA	De 0,01 à 10%
LESSIVE SOUDE	De 0 à 1 %
CONSERVATEURS	De 0 à 1 %
ACIDE CITRIQUE	De 0 à 1 %
EAU PURIFIÉE	QSP 100 %

Milk for dry skin, atopic

HUILE AMANDE DOUCE	De 1 à 5 %
HUILE MAIS	De 1 à 5 %
ACIDE STEARIQUE	De 1 à 5 %
ALCOOL CETYLIQUE C16 C18	De 0 à 1 %
ANTIMOUSSE 70414	De 0 à 1 %
ALCOOL LAURIQUE 11OE	De 1 à 5 %
MONOLAURATE PEG 300	De 0 à 1 %
MONOLEATE DE GLYCEROL	De 0 à 1 %
MONOSTEARATE DE GLYCEROL	De 1 à 5 %
VITAMINE B12	De 0 à 5 %
	De 0,1 à 10 %
CONCENTRAT D'HUILE DE TOURNESOL	De 0,01 à 10 %
PEPTIDES DE LUPIN	De 0,01 à 10 %
CONSERVATEURS	De 0 à 1 %
ACIDE CITRIQUE	De 0 à 1 %
CITRATE TRISODIQUE	De 0 à 1 %
EAU PURIFIEE	QSP 100 %
PARFUM	De 0 à 1 %
HUILE ARACHIDE	De 1 à 5 %
HUILE PALMISTE HYDROGENEE	De 1 à 5 %

The product shall be so manufactured as to conform to the requirements of this Regulation.

CAPRYLO CAPRATE DE GLYCEROL	De 5 à 20%
CYCLOPENTASILOXANE	De 10 à 20%
DICAPRYLYL CARBONATE	De 5 à 20%
TINOSORB S	De 1 à 10%
OXYDE DE TITANE 100	De 10 à 20%
HECTORITE	De 0 à 5%
ALPHA TOCOPHEROL	De 0 à 2%
LAURYLGLUCOSIDE-GLYSTEARATE	De 0 à 10%
EAU PURIFIÉE B4	QSP 100%
ACIDE CITRIQUE	De 0 à 2%
PENTYLENE GLYCOL	De 0 à 5%
GLYCEROL	De 0 à 5%
GOMME XANTHANE	De 0 à 2%
ALOE VERA	De 0 à 1%
GLUCONATE ZINC	De 0 à 1%
CONSERVATEURS	De 0 à 2%
TINOSORB M	De 1 à 10%

5. Examples of formulations of oral formulations

Arabinogalactan and Lupin peptides are incorporated into oral formulations, in formulations allowing administration of 50 mg to 200 mg daily.

1/ Redness-reducing formula in the form of soft capsules

- ARABINOGALACTANE	30 mg
- PEPTIDES DE LUPIN	30 mg
- Huile d'Awara	60 mg
- Huile de colza riche en insaponifiable	300 mg
- Vitamine du groupe B (B1, B2, B3, B5, B6, B9, B12),	QSP 100% des AJR
- Tocotriénols	QSP 50 % AJR
- Vitamine E
- Cire d'abeille
- Lécithine de soja
- Gélatine alimentaire
- Glycérine QSP 1 capsule molle

This is given as 4 to 6 500 mg capsules per day.

2/ Examples of stick-based soothing powder

100 mg
- PEPTIDES DE LUPIN	100 mg
- Extrait de thé riche en polyphénols	100 mg
- Extrait de raisin riche en OPC	50 mg
- Bétaglucanes d'origine végétale	100 mg
- Gomme xanthane	1 mg
- ascorbate de sodium	0,3 mg
- maltodextrine	QSP 5 g.

This composition is administered twice daily.

References to the text

The study was conducted by the University of California, Irvine, and was funded by the National Institutes of Health (NIH).[1] Yamasaki K and Gallo RL. The molecular pathology of rosacea. 2009, J Dermatol Science; 55:77-81.[2] Koczulla R, von Degenfeld G, Kupatt C, Krotz F, Zahler S, Gloe T et al. An angiogenic role for the human peptide antibiotic LL37/hCAP-18. 2003, J Clin Invest; 111:1665-72.[3] Rodriguez-Martinez S, Cancino-Diaz JL, Vargas-Zuniga LM, Cancino-Diaz ME. LL-37 regulates the overexpression of vascular endothelial growth factor (VEGF) and c-IAP-2 in human keratinocytes. 2008, J Dermatol; 47:457-62.[4] Yamasaki K, J Auber, Linda, Horsch, Drin, Schechter and al. Coheins regulated the antimicrobial effects of the cat in 2006, J FAS 2068-80.The expression of TLR2 is increased in Rosacea and stimulates enhanced serine protease production by keratinocytes. 2011, Dermatol; 131:688-697[7] Bevins CL and Liu FT. Rosacea: skin immunity is gone, 2007, Nat Med; 13904-906[8] Guzman-Sanchez Dauji, Ishi Y, Patel T, Fountain J, YH, Yoshi G. Hipovitch and blood flow and enhanced sensitivity to heat in rosacea are noxious papules.The study was funded by the National Institutes of Health (NIH), the National Institutes of Health (NIH), the National Institutes of Health (NIH), the National Institutes of Health (NIH), the National Institutes of Health (NIH), the National Institutes of Health (NIH), the National Institutes of Health (NIH), the National Institutes of Health (NIH), the National Institutes of Health (NIH), the National Institutes of Health (NIH), the National Institutes of Health (NIH), the National Institutes of Health (NIH), the National Institutes of Health (NIH), the National Institutes of Health (NIH), the National Institutes of Health (NIH), the National Institutes of Health (NIH), the National Institutes of Health (NIH), the National Institutes of Health (NIH), the National Institutes of Health (NIH), the National Institutes of Health (NIH), the National Institutes of Health (NIH), the National Institutes of Health (NIH), the National Institutes of Health (NIH), the National Institutes of Health (NIH), the National Institutes of Health (NIH), and the National Institutes of Health (NIH).Hanakawa et al. Induction of keratinocyte migration via transactivation of the epidermal growth factor receptor by the antimicrobial peptide LL-37. 2005, J Immunol; 175:4662-8.

Claims (13)

1. Composition comprising arabinogalactan for use in the prevention and/or treatment of redness of the skin in individuals likely to form or experience redness.
2. Composition for use according to claim, 1 characterised in that said composition is administered topically.
3. Composition for use according to claim 1, characterised in that said composition is administered orally.
4. Composition for use according to any of claims 1 to 3, characterised in that the arabinogalactan is extracted from larch.
5. Composition for use according to any of claims 1 to 4, characterised in that the arabinogalactan is present in said composition in a proportion of between 0.01% and 10% by weight in relation to the total weight of the composition.
6. Composition for use according to any of claims 1 to 5, characterised in that said composition comprises at least one other anti-redness agent selected from the group consisting of: lupin peptides, permethol, genistein, esculoside, dextran sulphate, hesperidin methyl chalcone, retinoids, licochalcone, oxymetazoline, kinetin, licorice extract, vitamin P-like substances, butcher's broom extract, Sophora japonica, Hamamelis extract, Ruscus, fucidic acid, penicillin, tetracyclines, pristinamycin, erythromycin, clindamycin, mupirocin, minocycline, doxycycline, polyphenols including tannins, phenolic acids, anthocyanins, procyanidols, flavonoids, green tea extract, red berries extract, cocoa extract, grape extract, Passiflora incarnata extract, and Citrus extract.
7. Composition for use according to claim 6, characterised in that said composition comprises arabinogalactan and lupin peptides.
8. Composition for use according to claim 7, characterised in that said composition comprises between 0.01% and 10%, preferentially 2% of arabinogalactan.
9. Composition for use according to claim 6, characterised in that said composition comprises between 0.01% and 10%, preferentially 0.2% of lupin peptides.
10. Arabinogalactan for use in preventing and/or treating outbreaks of redness of the skin.
11. Combination of arabinogalactan and of lupin peptides to prevent and/or treat outbreaks of redness of the skin.
12. Composition comprising arabinogalactan for use in prevention and/or treatment of rosacea.
13. Composition containing arabinogalactan and lupin peptides for use in the prevention and/or treatment of rosacea.