FR3095591A1 - Combination of an extract of Uncaria tomentosa liana and an extract of oat seedlings to modulate the pathways of nociception - Google Patents

Abstract

The invention relates to a novel combination of an extract of liana uncaria tomentosa and an extract of oat seedlings and its uses in neurogenic skin inflammation, and in the modulation of nociception pathways, in particular due to inflammatory dermatoses. .

Description

Combination of an Uncaria tomentosa liana extract and an oat seedling extract to modulate nociception pathways

The invention relates to a new combination of an Uncaria Tomentosa liana extract and an oat seedling extract, as well as the use of said combination in the protection and/or treatment of the skin which presents sensations of discomfort and/or irritated skin, or skin affected by an inflammatory dermatosis. This association has the ability to modulate the pathways of nociception. The beneficial effect of this combination is due to a targeted action on neurogenic cutaneous inflammation. The invention also relates to cosmetic or dermatological compositions comprising such a combination.

The epidermis is a multi-stratified epithelium that performs a protective barrier function against its environment and its aggressions. Among its multiple physiological functions, the epidermis has that of constituting a biological, physical and chemical barrier against the invasion of the body by microorganisms. This physical barrier property of the epidermis is particularly linked to its structure. Thus the epidermis is conventionally divided into a basal layer of keratinocytes constituting the germinal layer of the epidermis, a so-called spiny layer consisting of several layers of polyhedral cells and finally, a set of upper layers called the horny layer (or stratum corneum), made up of keratinocytes at the terminal stage of their differentiation called corneocytes. The chemical barrier properties of the epidermis depend in particular on the release on the surface of the latter of numerous antimicrobial peptides. A dysfunction of the epidermal cellular structural organization, or a defect in the chemical barrier function of the epidermis, can result in a cutaneous inflammatory state.

The skin is an organ whose innervation is very dense and goes to the most superficial layers, with the exception of the stratum corneum. The epidermis is also characterized by numerous free nerve endings up to the outermost layers. These nerve endings come from sensory neurons from the spinal ganglia located along the spinal cord. These neurons therefore have extremely long axons that transmit sensory information: tactile, heat but also pain, from the skin to the brain. The density of innervation varies according to the area of the body. Thus, in humans, the hands and face are richly innervated compared to the back or abdomen.

There are sensory fibers and autonomic nerve fibers in the skin, both of which belong to the peripheral nervous system. Sensory type nerve endings respond to a variety of physiological stimuli such as heat, cold, touch, mechanical distension and UV. Some fibers can even be activated by a variety of chemical substances or by biological factors such as microbiological agents or proteases from plants.

Everyone has experienced pain. Pain is not a disease, but a warning. Known pain of short duration is considered normal. Indeed, pain is an alarm signal that informs the body. It is defined by the IASP (International Association for the Study of Pain) as “an unpleasant sensory and emotional experience in response to existing or potential tissue damage”. This definition clearly explains that everyone has their own experience of pain. This can range from acute pain, such as from a needle or cut, to chronic pain from a persistent problem, such as arthritis. All parts of the body of course can be subject to pain, in particular acute pain, the skin is not spared. Pain in the skin tissue can take different forms: burning, stinging, electric shocks, tingling, itching, etc. In addition, some unexplained, more recurrent skin pain can be due to neuropathies, we speak of small fiber neuropathies. They could be responsible for unexplained pain manifesting in the form of tingling, tightness when the skin is normal: we speak of allodynia.

Allodynia is pain triggered by a stimulus that is normally painless. For example, a slight touch of the skin or a weak sensation of hot or cold can then be painful.

Neurons that respond selectively to stimuli generated by tissue damage are called nociceptors. They are made up of Aδ and C fibers. The Aδ fibers are mainly mechano-nociceptors which are involved in well localized acute pain. C fibers are polymodal nociceptors that are involved in dull, poorly localized pain.

Between the peripheral pain message and the perception of pain, there is thus an electrical and chemical cascade which is divided into four distinct stages:

– transduction is the coding of the sensory message for the delivery of nociceptive information to the posterior horn of the spinal cord. The transduction is carried out by channel receptors which depolarize the free terminal of the nociceptors, thus activating voltage-dependent sodium channels (NaV1.6 – 1.9) allowing the generation and propagation of action potentials. At the level of the central termination of the nociceptor in the posterior horn of the medulla, the action potentials will cause the entry of calcium which will allow the release of numerous neuromodulators and signaling molecules into the synaptic cleft. At this level, there is a modulation of the nociceptive signal of the excitatory or inhibitory type;

- transmission, the nociceptive action potential travels in the nociceptor to the dorsal horn of the spinal cord where it will be transmitted to a second-order spinothalamic neuron. The secondary neuron immediately crosses into the medulla passing under the ependymal canal to form the spinothalamic pathway ventrolateral to the medulla and conducts information to different regions of the ventrobasal and centromedial complexes of the somatosensory thalamus where it will make a synaptic contact with the third neuron;

- modulation is the set of mechanisms by which the nervous message of nociceptors can be modulated at the spinal level but also at the central level. In particular, there are descending inhibitory controls from the brainstem that act on the spinal transmission of nociceptive messages. After peripheral nociceptive stimulation, a diffuse nociceptive inhibitory control comes into play coming from numerous regions of the brainstem and involving the noradrenergic, serotonergic and enkephalinergic pathways; And

– the perception of pain is effective when the nociceptive information reaches the brain through the thalamocortical pathways. The third or thalamo-cortical neuron then conducts nociceptive information to different regions of the somatosensory cortex and certain limbic structures. The higher pain centers allow one to realize the complexity of the balance between the sensory/discriminative and affective/emotional components of pain. The activation of the prefrontal cortex could be related to the cognitive aspects of pain perception.

The sensation of skin pain is relatively common, as around one in 3 people would be affected. It is important to note that 60% of patients who complain of skin pain have dermatosis. Furthermore, about 50% of patients with dermatosis report having skin pain, whereas only 10-15% of patients without dermatosis report having skin pain. It appears that the main painful dermatoses are atopic dermatitis, eczema and psoriasis, rosacea and reactive skin, i.e. fragile, intolerant skin. The characteristics of the pain experienced by patients are mainly itching, burning sensation, tingling.

Millions of people are affected by these skin pains, in France nearly 4 million people complain of skin pains and suffer from atopic dermatitis, psoriasis or contact eczema.

Inflammatory dermatoses are affections of the skin and mucous membranes, often painful, which are characterized by unsightly manifestations such as redness and patches of desquamation. Several pathologies are grouped together under the name of inflammatory dermatoses. Mention may be made, by way of non-limiting examples, of: atopic dermatitis, eczema, psoriasis, rosacea, lichen planus, prurigos, seborrheic dermatitis or even acne. These dermatoses very often result from inflammatory phenomena and immune disorders.

Atopic dermatitis is the cutaneous manifestation of atopy. It is a chronic inflammatory dermatosis, occurring on a genetically determined ground. It affects 15 to 30% of children and 2 to 10% of adults. Its prevalence is steadily increasing in industrialized countries; it has doubled, even tripled, over the past three decades and is now considered a major public health concern. Atopic dermatitis is often associated with other atopic disorders, such as allergic rhinitis and asthma. This condition most often appears during early childhood and is characterized by repeated eruptions over several years. It evolves by relapses interspersed with spontaneous remissions. The lesions are characterized by severe skin dryness associated with inflammatory manifestations: erythematous papular, vesicular, scaly and very itchy eruptions. Histologically, atopic dermatitis is characterized, like many dermatoses, by an infiltration of lymphocytes, monocytes and polymorphonuclear eosinophils around small vessels and capillaries; biochemically, it is characterized by the expression of cytokines such as Thymic Stromal Lymphopoietin (TSLP), a major protein in triggering the inflammation associated with atopic dermatitis. Furthermore, it has been shown that chemokines, in particular interleukin 8 (IL8) and lipid mediators of inflammation such as prostaglandin 6KF1α, are strongly implicated in dermatoses such as atopic dermatitis and in chronic inflammatory diseases. in general.

Eczema is an itchy dermatosis characterized by inflammation of the skin that is accompanied by redness, fine vesicles, scales and itching. It can start very early in life, it is even observed in infants. Affected individuals experience periods commonly referred to as "eczema flare-ups", during which symptoms worsen. These relapses, of variable duration, are interspersed with periods of remission. Eczema is a genetic disorder, but environmental factors such as the presence of chemical irritants or stress influence its appearance.

Psoriasis, an inflammatory skin disease par excellence, is characterized by the appearance of thick patches of peeling skin. These plaques are present in different places on the body, most often on the elbows, knees and scalp. This chronic disease evolves in cycles, with periods of remission. Psoriasis can be very unpleasant or even painful when it appears on the palms of the hands, the soles of the feet or in the folds of the skin. There are several types of psoriasis, the most common form being plaque psoriasis or psoriasis vulgaris. The other forms are guttate, erythrodermic and pustular psoriasis.

Rosacea is a common chronic and progressive inflammatory dermatosis linked to vascular relaxation. It is a condition that affects the small vessels of the face. It frequently affects fair-skinned people and can have significant psycho-emotional consequences. The name of this pathology refers to the characteristic color that the face takes on during the disease.

Lichen planus is an itchy rash that only affects adults. It is an inflammatory skin condition of unknown origin. This dermatosis affects the skin, the mucous membranes but also the hair and the nails.

Prurigo is an intense pruritus of the skin with erythematous and vesicular papules with scratching lesions. It is most often an exaggerated sensitivity to insect bites, sensitivity that lasts abnormally long and is common especially in young children.

Seborrheic dermatitis is a chronic inflammatory skin condition that affects areas rich in sebaceous glands, namely the scalp and face. It is due to a yeast, Malassezia, present in the skin and which develops in the sebum. This condition evolves in flare-ups favored by stress, lack of sun and pollution.

Acne is a common skin pathology, the result of inflammation of the pilosebaceous follicles due largely to the colonization of Cutibacterium acnes in the infundibulum.

Inflammation is a normal immune defense reaction of the body to an attack of the type: infectious, thermal, mechanical, chemical, lesional or even allergic. It is characterized in four points which are: redness, heat, swelling and pain.

Acute skin inflammation is an immediate response to an aggressor, short-lived (a few days or weeks), often sudden onset and characterized by intense swelling. Acute inflammations heal spontaneously or with treatment. Chronicity appears when the inflammation does not heal spontaneously, persists or worsens for several months or even several years. The inflammatory reaction is a dynamic process comprising several successive stages: vascular (vasodilatation), diapedesis of leukocytes and chemotaxis of immune cells and finally debridement. Leukocyte diapedesis corresponds to the active crossing of the vascular walls by leukocytes and the accumulation of circulating immune cells, lymphocytes, neutrophils and monocytes in the lesion focus. Neutrophils function to attract other inflammatory cells by chemotaxis and to clean the injured site by secreting antimicrobial substances and proteases. Monocytes migrate by chemotaxis and differentiate into macrophages cleaning the injured area. They secrete growth factors, inflammatory cytokines, such as IL-1, in particular IL-1β, TNFα, proteases, prostaglandins and IFNs allowing the maintenance and/or amplification of inflammation. The debridement is consecutive to the vascular phase and contemporary with the leukocyte diapedesis. This is the elimination of necrotic tissue and pathogens.

Cutaneous neurogenic inflammation is defined as the induction and/or amplification of a primary inflammatory process by nerve endings, thus it is an inflammation of the skin induced by the activation of nerve fibers intra- epidermal which secrete neuropeptides such as substance P. Neurogenic cutaneous inflammation is particularly involved in irritated skin, skin presenting feelings of discomfort, even in skin affected by inflammatory dermatoses, in particular pruriginous. Pruritus is defined as an unpleasant sensation that causes the urge to scratch. The notion of pruriceptors has recently emerged, in particular specific for perceiving pruritus, but their distinction from the family of nociceptive receptors is still debated. These pruriceptors use intra-epidermal fibers of type Aδ and especially those of type C. They secrete neuropeptides: substance P, calcitonin gene related peptide (CGRP) and vasoactive intestinal peptide (VIP). Recently, the role of proteases (trypsin, cathepsin G, thrombin etc.) in the induction of pruritus has been clearly established. Indeed, their PAR-2 receptor has been defined as the second major pathway for pruritus activation (Misery et al., Nat. Rev. Neurol. 10, 408-416, 2014).

Intradermal nerve fibers interact directly or indirectly with skin cells and cells of the endocrine, lymphatic and immune systems. These communications led to the definition of a neuro-immuno-endocrine-cutaneous system. To function, this system requires a common language made up of molecules of different natures: neuromediators, cytokines and growth factors. These molecules are synthesized and released by skin cells, resident and recruited immune cells, and intraepidermal nerve endings. Epidermal and dermal cells can also produce neurotransmitters, enzymes, neurotrophins, cytokines, chemokines, and growth factors. These mediators regulate cutaneous innervation and the inflammatory response. In the event of inflammation, the immune cells in transit or present constitutively in the skin, can be activated under the action of these mediators secreted by the sensory nerve endings and the cells of the skin. This process leads to a second wave of release of cytokines and neuromediators, which generate an amplification loop of inflammation.

A new concept has recently emerged, suggesting that keratinocytes are also major players in neurogenic skin inflammation.

Neurogenic skin inflammation generated by neuropeptides is involved in the reactivity of irritated skin. The notion of irritation reflects the level of sensitivity of each. While it is possible to have irritated skin at any age, it is extremely common in babies and the elderly. Baby skin is about one-fifth the thickness of adult skin and is therefore extremely sensitive to chemical, physical and microbial attack, as well as UV rays. The barrier function of adult skin, on the other hand, gradually weakens with age, along with the slowing down of metabolic processes. The aging of the skin gradually leads to a deficiency in lipids, which makes it more easily irritated by alkaline substances such as soap.

Besides inflammatory dermatoses, skin pain is common in patients with reactive skin, which reacts to stimuli that have no effect on other types of skin. This hyper-reactivity of the skin results from a reduction in its tolerance threshold. The more reactive the skin, the lower the threshold.

Hyper-reactive skin or very reactive skin is a condition of the skin, unpleasant to live by the people who are affected by it, but very common and which can cause visible skin reactions such as dry skin, redness, flaking. But it can also cause invisible and therefore subjective reactions, described among other things as feelings of burning, itching, tightness or tingling.

Painful skin is defined as skin that is the seat of unpleasant cutaneous sensations, namely tingling, itching, burning sensations, sometimes in reaction to various aggressions of varying intensities that would be well tolerated by normal skin. A more extreme and common version of painful skin is hypersensitive skin characterized by unpleasant feelings of discomfort and visible reactions when in contact with external or internal stimuli, which would ordinarily be harmless, such as extreme temperatures, chemicals or UV radiation. These sensations and their intensity vary from person to person, which makes the diagnosis all the more difficult.

Three signs are commonly observed in people with painful skin: an altered skin barrier, very reactive sensory fibers in the epidermis and redness.

The altered skin barrier also causes trans-epidermal dehydration which makes the skin more sensitive to the penetration of irritating external factors.

The sensory fibers of a painful, hyper-reactive or over-stimulated epidermis react faster and more markedly than those of normal or non-painful skin. These sensory fibers trigger unpleasant skin sensations which are described as, among other things, sensations of tingling, heating or tightness of the skin of the face or scalp without any visible signs being observed. In the most severe cases, the invisible signs are accompanied by skin dryness, rash or redness.

Reactions on irritated skin, or showing feelings of discomfort, can be triggered by environmental, psychological, external and/or mechanical factors, as mentioned below without limitation. Environmental factors include sudden changes in temperature, heat, cold, wind, sun, and air pollution. Psychological factors include strong emotions, stress. External factors include exposure to certain cleaning products, spicy food, alcohol, perfumes, detergents, swimming pools, excessively hard water, baths and showers. Mechanical factors involve pressure on the skin.

Preventing skin pain or treating it requires several solutions. There are dermal compositions containing local anesthetics such as for example butoform, ethoform or other products with equivalent functions. However, contact anesthetics often have the disadvantage of causing general sensitization and not just local sensitization as desired. In addition, they are frequently responsible for allergic reactions whose degrees of severity can range from simple dermatitis to anaphylactic shock.

In addition, analgesics or analgesics are drugs intended to reduce pain. There are 3 levels defined according to their activity. Level 1 concerns paracetamol and nonsteroidal anti-inflammatory drugs, such as aspirin, ibuprofen, noramidopyrine, which are prescribed first in the event of mild to moderate pain. They act mainly by inhibition of cyclo-oxygenase. Level 2 concerns weak opiate analgesics such as codeine, dihydrocodeine, tramadol. This type of substance acts in the brain on specific receptors responsible for the abolition of pain. Level 3 concerns strong opioid analgesics such as morphine and its derivatives. They are used in case of intense pain or pain resistant to level 2 analgesics. All these analgesics have side effects, ranging from gastric problems to causing addiction problems.

Alongside all these drugs there are gentler solutions, we can mention certain plants and homeopathic strains, such as arnica which has demonstrated its anti-inflammatory and analgesic properties, especially if it is administered within minutes of the shock.

There are also sprays without therapeutic molecules, which provide instant cold that anesthetizes the pain. The cold allows the contraction of the vessels and prevents the diffusion of blood. Cold, via mechanoreceptors and/or TRPM8 activation, stimulates interneurons to modulate nociception pathways as counterstimuli at the level of the spinal cord dorsal horn. These sprays may contain gases commonly used in cryotherapy, such as butane, isobutane, propylene, methylal. They have the disadvantage of containing propellants, which are flammable and critical.

There is a real need to have new cosmetic or dermatological compositions for soothing topical use, making it possible to reduce skin irritations, feelings of discomfort, or even useful for modulating the pathways of nociception, or relieving skin pain.

The inventors have surprisingly demonstrated that a combination of an Uncaria Tomentosa liana extract and an oat seedling extract is capable of modulating the nociception pathways in a synergistic manner.

The subject of the present invention is a new combination comprising an extract of Uncaria Tomentosa liana and an extract of oat seedlings.

Another subject of the present invention relates to this combination for use, in particular topical use, for the prevention and/or treatment of neurogenic cutaneous inflammation.

In particular, the prevention and/or treatment of neurogenic cutaneous inflammation includes, or consists of, the protection and/or treatment of irritated skin or fragile skin.

Another object of the present invention relates to this combination for use, in particular topical use, for modulating the pathways of nociception.

Another object of the present invention relates to this combination for use, in particular topical use, for the prevention and/or treatment of itching sensations and/or skin pain.

According to a particular embodiment of the invention, the itching and/or skin pain are due to inflammatory dermatoses, in particular atopic dermatitis, eczema, psoriasis, rosacea, lichen planus, prurigo, seborrheic dermatitis or acne.

According to another particular mode of the invention, the itching and/or the skin pains are due to a prick, a blow, or to a medical or surgical act, in particular an excision.

Another object of the present invention relates to this combination for use, in particular topical, for the prevention and/or treatment of inflammatory dermatoses, in particular chosen from atopic dermatitis, eczema, psoriasis, rosacea, lichen planus, prurigos, seborrheic dermatitis or acne.

Another object of the invention relates to the use of the combination according to the invention for preventing and/or treating neurogenic cutaneous inflammation.

Another object of the invention relates to the use of the combination according to the invention to modulate the pathways of nociception.

Another object of the invention relates to the use of the combination according to the invention for preventing and/or treating the sensations of itching and/or skin pain.

Another object of the invention relates to the use of the combination according to the invention for relieving, soothing or calming irritated skin and/or fragile skin and/or painful skin.

A subject of the invention is also the use of the combination according to the invention for the manufacture of a pharmaceutical or dermatological composition intended to prevent and/or treat neurogenic cutaneous inflammation.

A subject of the invention is also the use of the combination according to the invention for the manufacture of a pharmaceutical or dermatological composition intended to relieve irritated skin and/or fragile skin.

A subject of the invention is also the use of the combination according to the invention for the manufacture of a pharmaceutical or dermatological composition intended to modulate the pathways of nociception.

The invention also relates to the use of the combination according to the invention for the manufacture of a pharmaceutical or dermatological composition intended to prevent and/or treat sensations of itching and/or skin pain, in particular itching. and/or skin pain due to an inflammatory dermatosis, a bite, a blow or a medical or surgical procedure.

The invention also relates to the use of the combination according to the invention for the manufacture of a pharmaceutical or dermatological composition intended to prevent and/or treat inflammatory dermatoses, in particular chosen from atopic dermatitis, eczema, psoriasis, rosacea, lichen planus, prurigos, seborrheic dermatitis or acne.

The invention also relates to a method for preventing and/or treating neurogenic cutaneous inflammation, comprising in particular topical administration to a patient in need of an effective amount of the combination according to the invention as described previously. .

The invention also relates to a method for relieving irritated skin and/or fragile skin, comprising in particular topical administration to a patient in need of an effective amount of the combination according to the invention as described above. .

The invention also relates to a method for modulating the pathways of nociception, comprising in particular topical administration to a patient in need of an effective amount of the combination according to the invention as described above.

The invention also relates to a method for preventing and/or treating sensations of itching and/or skin pain, in particular itching and/or skin pain due to an inflammatory dermatosis, a bite, a blow or an act medical or surgical, comprising in particular topical administration to a patient in need of an effective amount of the combination according to the invention as described previously.

The invention also relates to a method for preventing and/or treating inflammatory dermatoses, in particular chosen from atopic dermatitis, eczema, psoriasis, rosacea, lichen planus, prurigos, seborrheic dermatitis or acne , comprising in particular topical administration to a patient in need of an effective amount of the combination according to the invention as described above.

In particular, the soothing, calming or relieving effect comprises or consists of a reduction in the sensations of cutaneous discomfort.

In particular, modulation of the nociceptive pathways includes or consists of less unpleasant skin sensation.

The Peruvian creeper or Uncaria tomentosa is a plant belonging to the Rubiaceae family. It is a climbing liana up to 20-30 m long, and the main stem reaches up to 25 cm in diameter. It has quadrangular, usually puberulous branches, broadly ovate-triangular stipules, finely and densely puberulous on the outside.

The leaves are glabrous or subglabrous, opposite, their lower surfaces are puberulous to pubescent, the blade is ovate to ovate-oblong, with the base rounded and the margin entire or crenate in the upper half. The thorns are located at the base of the leaves, strongly curved, hairy on the young branches, glabrous on the older ones. It is these thorns that help the plant to climb trees, usually 20 to 40 meters, hence the name "cat's claws".

The inflorescence bears reduced bracts, with small heads 12-20 mm in diameter, peduncles 1.5-4 cm long. The flowers are sessile with a tubular calyx, with obtuse lobes. The sessile fruits are capsules, 0.8 to 1.2 cm long, pubescent on the outside. The seeds have two long wings and are narrow.

There are 34 species of Uncaria with medicinal properties.

Uncaria tomentosa is a South American plant that was widely used by primitive peoples, especially in Peru. It is the roots or stem bark that are used medicinally both orally and topically. Many treatments are the subject of the use of this plant: rheumatism, arthritis, gastric ulcers, fever, asthma, urinary tract infections, viral infections, allergies. These indications involve an inflammatory process and/or an immune disorder. Clinically it has been recognized beneficial effects of Uncaria tomentosa against leukemia, tumors, ulcers, infections and arthritis.

Three classes of constituents play an important role in the activity of Uncaria tomentosa : alkaloids, polyhydroxylated triterpenes and polyphenols.

From a therapeutic point of view, the most important constituents in the stem bark of Uncaria are the indole alkaloids, especially those with a pentacyclic structure (pteropodine, 25% of the total alkaloid, isopteropodine, speciophylline, uncarine F, mitraphylline and isomitraphylline). Quantitatively, the most important tetracyclic alkaloids are rynchophylline and isorynchophylline.

Among the sterols, b-sitosterol predominates, followed by stigmasterol and campesterol. Several triterpenes have been isolated from the bark and stem of Uncaria tomentosa , ursolic acid, oleanolic acid, uncaric acid, floridic acid, two trihydroxy-ursenoic acids, dioxo-ursenoic acid, several quinovic acid glycosides, tomentosides A and B.

For polyphenols, tannins and procyanidins have been identified, as well as kaempferol and dihydrokaempferol. Among the flavonoids isolated there are epicatechin and cinchonaines Ia and Ib. p-coumaric acid.

At the pharmacological level, two main activities are well described: an anti-inflammatory activity and an analgesic activity. For the anti-inflammatory side, decoctions of Uncaria bark inhibit the production of TNF _α and to a lesser extent that of PGE ₂ (Goncalves et al., 2005, Phytochemistry, 66(1), 89). The aqueous extract of the bark of Uncaria tomentosa shows anti-inflammatory activity which would be due at least in part to a glycoside of quinovic acid. This extract attenuates chronic intestinal inflammation induced by indomethacin in rats. It inhibits the activation of the NF _{κ B} factor by 65 to 85% and it is active in arthritis, alone or as an adjuvant to traditional therapies to treat pain, stiffness and inflammation. By comparing an aqueous extract and an 80% ethanolic extract of the bark, it was found that the anti-inflammatory activity was significantly greater for the hydroalcoholic extract. Mitraphylline, a pentacyclic oxindolic alkaloid present in the chloroform extract of the bark of Uncaria , has been evaluated in vivo on various cytokines which play a role in inflammation. It inhibits the release of interleukins 1α, 1β, 17 and TNF _{- α} by 50% in the same way as dexamethasone. Mitraphylline reduces IL-4 production by 40% unlike the corticosteroid which has no activity (Rojas-Duran et al., 2012, J. Ethnopharmacol. 143(3), 801-804). A clinical study carried out for 52 weeks, on 40 patients suffering from rheumatoid arthritis, having received 3 times 20 mg of aqueous extract of Uncaria tomentosa per day, containing 73.5% of pentacyclic alkaloids, without tetracyclic alkaloid, in double blind versus placebo, showed a significant improvement in their symptoms (painful joints and morning stiffness). However, there was no effect of the treatment on the swollen joints and on the patient's perception of the progress of his disease.

With regard to pain, an alkaloidal fraction of Uncaria tomentosa showed antinociceptive activity in vivo after intraperitoneal administration (Jurgensen et al., 2005, Pharmacology, Biochemistry and Behaviour, 81:466-477). The main results are a suppression of acute pain induced by capsaicin and the response to abdominal acetic acid. With a formalin test, pain inhibition is found in both early and late phase. One of the putative mechanisms of action is the activation of 5HT-2 receptors. The alkaloids geissoschizine methyl ether and isorhynchophylline showed 5-HT1A agonist and 5HT2A/2C antagonist activity.

The plant comes exclusively from organized collection, carried out in Peru, it takes 3 years for the vine to be productive. The aerial part is harvested several times a year on the same plant, leaving about 50cm of stem for the renewal of the plant. Debarking, which takes place on the harvesting site, is followed by bundles of bark of about 1m. Drying is carried out in the sun on a concrete slab or on a plastic sheet for 4 to 5 days depending on the season.

According to one embodiment of the invention, the extract of Uncaria tomentosa is a liquid extract, more particularly a hydrophilic extract, more particularly still an aqueous extract and even more particularly a hydroalcoholic or hydroglycolic extract.

This extract may in particular be obtained by extraction with at least one hydrophilic solvent, preferably with at least one aqueous solvent and even more preferably with at least one hydroalcoholic solvent.

Such an extract may be used as it is (solution with the extraction solvent) or in the form of a concentrated extract or a dry extract after partial or total evaporation of the extraction solvent.

According to a preferred embodiment of the invention, when the extract is an aqueous-alcoholic extract, the alcohol is evaporated and the aqueous solution obtained is stabilized by adding propylene glycol.

In one embodiment of the invention, the oat extract is obtained from oat seedlings, and preferably as described in WO 2010/054879.

By "oat seedlings" is meant within the meaning of the present invention the oats before heading, that is to say at the stage after germination (about 2 weeks to 2 months after germination) during the stage of bolting up to earing not included. The growth phase which corresponds to the elongation of the stem and the rise of the ear in formation, before flowering, is called "bolting". Secondary metabolites are described in application WO 2010/054879 as components of an oat seedling extract: flavonoids and saponins of the avenacoside type. Said extract is characterized by the presence of 2 to 15% of flavonoids and 0.2 to 2% of avenacosides A and B.

The process for preparing oat extract can be as follows:

– drying and grinding of oat parts, preferably oat seedlings,

– extraction in organic solvent chosen from the group consisting of ketones, esters, C1 to C4 alcohols and mixtures in any miscible proportion of these solvents, and

– centrifugation or filtration.

Advantageously, the organic solvent of the process according to the invention is chosen from the group consisting of acetone, methyl ethyl ketone, methyl isobutyl ketone, ethyl acetate, a C1 to C4 alcohol and a mixture in any proportion miscible with these solvents.

The marc obtained by the extraction step is then separated from the extract by centrifugation or filtration and the solution can be more or less concentrated until a dry extract is obtained.

According to one embodiment of the invention, a support can be added during the drying step in mass proportions relative to the extracted dry matter which can vary from 1 to 75%. The support can be a sugar such as maltodextrin, lactose, silica or any other cosmetologically or dermatologically acceptable support.

In another embodiment of the invention, the solution is concentrated so as to obtain a must comprising from 60 to 80% of dry matter, and preferably 70% of dry matter, by weight relative to the total weight of the must.

According to another embodiment, the invention relates to a cosmetic or dermatological composition comprising, as active principle, a combination according to the invention according to a mode described above and at least one cosmetically or dermatologically acceptable excipient, more particularly suitable for topical application. .

In a particular embodiment, the combination according to the invention is the only active principle on neurogenic cutaneous inflammation or modulator of the nociception pathways of the composition.

In the present invention, the term "cosmetically or dermatologically acceptable" is intended to denote what is useful in the preparation of a cosmetic, dermatological composition, which is generally safe, non-toxic and neither biologically nor otherwise undesirable and which is acceptable for a cosmetic or dermatological use, in particular by topical application to the skin.

By “topical application”, is meant an application to the skin, the mucous membranes, and/or the superficial body growths.

The invention preferably relates to cosmetic or dermatological compositions according to the invention which are presented in a clean form and suitable for topical application.

The cosmetic or dermatological compositions according to the invention may thus be in the forms which are usually known for topical administration, that is to say in particular lotions, shampoos, balms, mousses, gels, dispersions , emulsions, sprays, serums, masks or creams, with excipients allowing in particular penetration in order to improve the properties and the accessibility of the active principles.

Advantageously, the composition according to the invention is administered in the form of a sprayable composition.

These compositions generally contain, in addition to the extracts of the combination according to the present invention, a physiologically acceptable medium, generally based on water or solvent, for example alcohols, ethers or glycols. They may also contain surfactants, complexing agents, preservatives, stabilizing agents, emulsifiers, thickeners, gelling agents, humectants, emollients, trace elements, essential oils, perfumes, colorants, moisturizing agents or thermal waters, etc.

Advantageously, the compositions according to the present invention comprise 0.01 to 10% by weight, preferably 0.05 to 5% by weight, preferably 0.1 to 3% by weight of Uncaria tomentosa liana extract, relative to the total weight of the composition.

Advantageously, the compositions according to the present invention comprise 0.01 to 5% by weight, preferably 0.05 to 3% by weight, more preferably 0.1 to 1% by weight of oat seedling extract, per relative to the total weight of the composition.

According to another embodiment, the invention relates to a cosmetic or dermatological composition according to the invention according to a mode described previously, for its use in the prevention and/or treatment of neurogenic cutaneous inflammation.

According to another embodiment, the invention relates to a cosmetic or dermatological composition according to the invention according to a mode described above, for its use as a modulator of the nociceptive pathways.

According to another embodiment, the invention relates to a cosmetic or dermatological composition according to the invention according to a mode described above, for its use in the prevention and/or treatment of itching sensations and/or skin pain, in particular itching and/or skin pain due to inflammatory skin disease, a bite, a blow or a medical or surgical procedure.

According to another embodiment, the invention relates to a cosmetic or dermatological composition according to the invention according to a mode described previously, for its use for relieving, calming or soothing irritated skin and/or fragile skin, and/or painful.

According to another embodiment, the invention relates to a cosmetic or dermatological composition according to the invention according to a mode described above, for its use in the prevention and/or treatment of inflammatory dermatoses, in particular chosen from atopic dermatitis, eczema, psoriasis, rosacea, lichen planus, prurigos, seborrheic dermatitis or acne.

According to another embodiment, the invention relates to the use of a cosmetic or dermatological composition according to the invention according to a method described above, to relieve, calm or soothe irritated skin and/or fragile skin, and/or painful skin.

Another object of the invention is the use of a cosmetic or dermatological composition according to the invention according to a method described above, to prevent and/or treat neurogenic cutaneous inflammation.

Another object of the invention is the use of a cosmetic or dermatological composition according to the invention according to a method described above, to modulate the pathways of nociception.

Another object of the invention is the use of a cosmetic or dermatological composition according to the invention according to a method described above, to prevent and/or treat itching sensations and/or skin pain, in particular itching and / or skin pain due to an inflammatory dermatosis, a bite, a blow or a medical or surgical procedure.

Another object of the invention is the use of a cosmetic or dermatological composition according to the invention according to a method described above, for preventing and/or treating inflammatory dermatoses, in particular chosen from atopic dermatitis, eczema, psoriasis, rosacea, lichen planus, prurigos, seborrheic dermatitis or acne.

Another object of the invention is a method for preventing and/or treating neurogenic cutaneous inflammation, comprising the administration to a patient in need thereof of an effective amount of a cosmetic or dermatological composition according to the invention according to a method described above.

Another object of the invention is a method for modulating the pathways of nociception, comprising the administration to a patient in need of an effective amount of a cosmetic or dermatological composition according to the invention according to a method described above.

Another object of the invention is a method for preventing and/or treating sensations of itching and/or skin pain, in particular itching and/or skin pain due to an inflammatory dermatosis, a bite, a blow or a medical or surgical act, comprising the administration to a patient in need thereof of an effective amount of a cosmetic or dermatological composition according to the invention according to a method described previously.

Another object of the invention is a method for preventing and/or treating inflammatory dermatoses, chosen in particular from atopic dermatitis, eczema, psoriasis, rosacea, lichen planus, prurigos, seborrheic dermatitis or acne, comprising the administration to a patient in need thereof of an effective amount of a cosmetic or dermatological composition according to the invention according to a method described above.

These cosmetic or dermatological compositions according to the invention can be used daily, once or several times a day, without limitation of treatment duration.

Examples

Example 1: Evaluation of an Uncaria tomentosa liana extract in a skin sensitivity model

The aim of this example is to evaluate the potential activity of an Uncaria Tomentosa vine extract on the modulation of the production of a cytokine (interleukin 8, IL-8) and vascular responses, after stimulation with substance P in an in vitro model of human explants.

The extract of Uncaria Tomentosa vine dissolved in 50% ethanol was tested at 10, 30 and 100µg/ml, in order to assess its potential effect in counteracting substance P. Several parameters were thus measured, the production of IL-8, the number of dilated vessels and the average surface of the capillaries, after histological analysis.

Fragments of normal human skin were obtained from 8 donors during plastic surgery. The fragments are placed in inserts, themselves positioned on wells in culture. The culture medium is specifically adapted to maintain these fragments in survival, it is added by the bottom of the well, a passage being carried out by a slow diffusion between the two compartments via a porous membrane. The vine extract is added to the culture medium of the skin inserts on D0 after 2 hours of rebalancing. Substance P is added at 10 μM for 24 hours of stimulation. On D2, the supernatants are recovered for IL-8 analysis, the skin explants are then fixed in paraffin for histological study. For each donor, a comparative study is conducted for the following 5 conditions:

– Fragment of untreated skin (control),

– Fragment of skin stimulated by substance P (group SP);

- Skin fragment stimulated by substance P in the presence of 10µg/ml of vine extract of Uncaria Tomentosa (Unc group 10);

- Skin fragment stimulated by substance P in the presence of 30µg/ml of vine extract of Uncaria Tomentosa (Unc group 30);

- Skin fragment stimulated by substance P in the presence of 100µg/ml of vine extract of Uncaria Tomentosa (Unc 100 group);

A cytokine immunoassay is performed with a reading at 450nm.

After staining with eosin-hematoxylin, vascular modulation is assessed by counting the number of dilated vessels over the entire histological section. This number is divided by the total number of vessels to calculate the percentage of dilated vessels. In addition, the morphometric analysis of the surface occupied by the lumen of the vessels is carried out to determine the average surface occupied in the dermis by the vessels.

An average of the results obtained from the 8 donors is calculated for each parameter. The statistical analysis consists of a two-tailed Student's t-test of paired measures.

The results on IL-8 production in ng/ml are summarized in Table 1 below:

Band Witness MS Unc 10 Unc 30 Unc 100 Mean 8.77 14.29 13.08 8.07 6.10 AND 6.88 6.73 8.65 7.25 4.60 stats vs SP P<0.01 - NS P<0.05 P<0.01

SD: standard deviation; NS: not significant.

Stimulation of skin fragments with substance P induces a significant increase (p=0.004) in the production of IL-8, compared with the control group (skin fragments without stimulation with substance P). In this model, the Uncaria Tomentosa extract induces a statistically significant decrease in the production of IL-8, p=0.015 and p=0.003 at the respective concentrations of 30µg/ml and 100µg/ml. A concentration-response effect is thus clearly demonstrated, with an initial concentration of Uncaria extract which does not allow a significant decrease in the production of IL-8 to be observed.

The results on the analysis of vessel dilation (% of vessels dilated) are summarized in Table 2 below:

Band Witness MS Unc 10 Unc 30 Unc 100 Mean 61.40 82.78 63.70 52.32 60.93 AND 12.35 8.65 21.93 19.30 19.45 stats vs SP P<0.001 - P<0.05 P<0.01 P<0.05

SD: standard deviation.

Treatment with substance P induces very marked vasodilation of the vessels (p=0.0001), compared with the control group. In the presence of Uncaria Tomentosa extract, this percentage of dilated vessels is significantly reduced, at the three concentrations tested.

The results on the surface analysis of the capillaries (µm²) are summarized in table 3 below:

Band Witness MS Unc 10 Unc 30 Unc 100 Mean 69.48 157.06 77.73 58.86 68.88 AND 28.76 86.91 45.21 28.99 33.06 stats vs SP P<0.05 P<0.05 P<0.05 P<0.05

SD: standard deviation.

Stimulation by substance P induces a significant increase in the mean surface occupied by the vessels compared to the control skin (p=0.018). In the presence of Uncaria Tomentosa extract, this average surface occupied by the vessels is significantly reduced, at the three concentrations tested.

In summary, the inventors have demonstrated that an extract of Uncaria Tomentosa in this study (human explant model) is capable of significantly reducing the three parameters evaluated in this model of neurogenic cutaneous inflammation produced by substance P. Thus the inventors demonstrate that an extract of Uncaria Tomentosa significantly reduces the neurogenic cutaneous inflammation produced by a neuropeptide, thus making it possible to emphasize that an extract of Uncaria Tomentosa has soothing properties.

Example 2: evaluation of an oat seedling extract in inflammation

The NF-κB transcription factor controls the expression of a large number of genes involved in the regulation of the inflammatory response. In its inactivated state, NF-κB resides in the cytoplasm with its protein IKB. Certain pro-inflammatory stimuli such as TNFα (Tumour Necrosis Factor α) and interleukin 1β induce the activation of NF-κB, in other words its nuclear translocation. Once in the nucleus, NF-κB induces the transcription of pro-inflammatory genes encoding cytokines, chemokines, adhesion molecules, growth factors and inducible genes such as cyclooxygenase 2 and NO synthase (Lauwrence et al., Nature Medicine, 7(12):1291-1297, 2001). It therefore seems that the nuclear factor NF-κB plays a key role in the initiation and amplification of the inflammatory response.

In the skin, keratinocytes actively contribute to inflammation. Some chronic inflammatory pathologies such as atopic dermatitis are characterized by a deregulation of inflammatory mediators expressed by keratinocytes. Skin lesions in patients with atopic dermatitis result locally from the expression of pro-inflammatory cytokines such as TNFα, IL-1β, which up-regulate NF-κB.

The aim of this study is to evaluate the potential soothing properties of an oat seedling extract, at the level of the activation of the transcription factor NF-κB stimulated by TNFα in human keratinocytes. The cell line used in this study is the HaCat line (human keratinocytes) stably transfected with the luciferase reporter gene.

The cells are cultured in DMEM medium (Dulbecco's Modified Eagle Medium) supplemented with fetal calf serum in an environment at 37° C. and 5% CO ₂ , on a 24-well plate. They are then pre-incubated for 60 minutes with the product to be tested, dissolved in water. A stimulating agent, TNFα (0.3 ng/ml, diluted in the culture medium) is added to the cultures which are then incubated for 5 hours at 37°C. In this study, the oat seedling extract is tested at 30, 100 and 300 µg/ml. The extract is prepared as follows: extract 10 g of oat seedlings with 100 ml of acetone/water (80/20) (v/v) extraction solvent, filter and rinse the marc with the solvent of extraction. Evaporate the acetone and resume the aqueous phase. Filter, concentration by drying until a dry extract is obtained.

A positive control is used in this test, it is dexamethasone (synthetic glucocorticoid hormone, with an anti-inflammatory and immunosuppressive effect) tested at 2µM diluted in water. It should be noted that 3 independent experiments were carried out. The Bright-Glo ^TM agent which induces cell lysis and which therefore allows the release of luciferase, and its substrate (luciferin) are added before reading the luminescence. The analysis of raw data is done with Microsoft Excel software. The inter-group comparison is carried out by a one-way ANOVA followed by Dunnett's post test.

The inhibition results (in percentage) of NF-κB activation (RLU) are summarized in Table 4 below:

Groups Design Exp 1 Exp 2 EXP 3 Avg Dexamethasone 2µM 45 53 37 45 Extract
dried oat seedlings 30µg/ml 7 5 20 11 100µg/ml 27 21 27 25 300µg/ml 43 39 40 41

Conc: concentration; Exp: experience; Avg: Average.

Stimulation with TNFα (0.3 ng/ml) does indeed induce the activation of NF-κB (results not shown). Dexamethasone (2 μM) used as an immunosuppressant inhibits this activation by 45% (p<0.001), which validates the reliability of this test.

The values given in the table show that the extract of oat seedlings inhibits in a concentration-dependent manner the activation of NF-κB induced by the stimulation of TNFα in human keratinocytes. All the concentrations tested are statistically significant, p<0.05 at the concentrations of 30 and 100 μg/ml and p<0.001 at the concentration of 300 μg/ml.

The inventors thus demonstrate that the extract of oat seedlings has soothing properties.

Example 3: effects of the combination of an extract of Uncaria tomentosa and an extract of oat seedlings on a model of sensory neurons

The aim of this study is to evaluate the modulating properties of an oat seedling extract, an extract of Uncaria tomentosa and their association in neurogenic skin inflammation.

To do this, the inventors have developed an in vitro experimental approach. An original model of human sensory neurons has been developed after cellular reprogramming of human pluripotent stem cells. This model makes it possible to study the inhibitory properties of the release of substance P by the compounds to be tested, studied after stimulation. This neuropeptide, substance P, being the main neuromediator involved in sensitization pathways in neurogenic inflammation, pain and pruritus.

The initial step is the reprogramming of human pluripotent stem cells by the successive use of different cocktails of growth factors. Phenotypic and morphological characterizations made it possible to verify the pattern of sensory neurons with in particular the expression of specific receptors such as TrKA, 5HT-2, P2RX3 or channels such as TRPV1, Nav1.7, Nav1.8, TRPM8 with colocalization with neuronal markers (Tuj1, Brn3A). These characterizations make it possible to establish a reprogramming period to reach an optimal pattern which is between D40 and D47 after the start of treatment with the growth factor cocktail.

Experimental conditions and treatment

The test is carried out on the model of sensory neurons in culture in a mixture of media (RPMI/N2/B27/Glutamax) in the absence (control conditions) or in the presence (treated groups) of the products to be tested. These two conditions are tested in the presence of Veratridine or in its absence. Veratridine (tested at 3µM, diluted in DMSO, final molar concentration 0.006%) is a polycyclic alkaloid extracted from the rhizome of the liliaceae Veratrum album. It causes persistent activation of voltage-gated sodium channels. Levels of the neuropeptide substance P are quantified 10 minutes after the addition of veratridine.

The sensory neurons are treated for 3 hours with either an oat seedling extract, or an Uncaria tomentosa vine extract, or the combination of these two extracts, and for 10 minutes under stimulation (by veratridine). Simultaneously, in another group, the sensory neurons are treated with lidocaine (a blocker of voltage-dependent sodium channels) at 100 μM (diluted in ethanol, final molar concentration 0.1%), used as a positive control. Each experimental condition is carried out on two batches of separate sensory neurons, and repeated at different times between D40 and D47 in order to have experiments at n=2.

The substance P released is measured in the incubation media of the untreated group (control) and of the groups treated after or without veratridine stimulation. It is quantified by Elisa according to the supplier's instructions.

The level of substance P (pg/ml) is calculated by interpolation from a standard curve. The raw data and the inhibition percentages are analyzed using Excel and GraphPad Prism software from Microsoft. The normality of the data was assessed by the Shapiro-Wilk and Kolmogorov-Smirnov normality tests. To validate the experiments, a paired t-test is performed between unstimulated and stimulated conditions. Finally, to validate the activity of the reference compound and the products tested, in particular the combination, inter-group statistical comparisons are carried out from the raw data by a one-way ANOVA associated with a Dunnett test as a post-test.

Results

Veratridine at 3 μM, as expected, strongly and significantly increases the release of substance P. Lidocaine, tested at 100 μM, significantly reduces the release of substance P induced by stimulation by veratridine. These expected results validate this test.

The inventors demonstrate that the combination of an oat seedling extract with an Uncaria tomentosa liana extract synergistically reduces the release of substance P stimulated by veratridine.

These results demonstrate the interest of using such an association in a dermatological or cosmetic composition in order to modulate the pathways of nociception.

Example 4: Preparation of the extract of Uncaria tomentosa

Uncaria tomentosa stem bark from Peru is ground and then extracted with a hydroalcoholic solvent (50% ethanol), under reflux and stirring. Once drained and filtered, the extracted solution is desolventized (the alcohol is evaporated), the aqueous solution obtained is stabilized by adding propylene glycol. A hydroglycolic extract containing about 2% dry matter, 49% water and 49% propylene glycol is thus obtained.

The polyphenols are dosed at 20% in the dry matter. The extract on support is standardized to 0.5% polyphenols. The alkaloids are dosed and are present at 5% in relation to the dry matter, i.e. 0.1% in the extract on support.

Example 5: Example of composition according to the invention

INCI designation Percentage
in weight Water QSP 100% Caprylic/Capric Triglyceride 2-20% Glycerin 2-10% Cross-Linked Polymer Acrylates/C10-30 Alkyl Acrylate 0.10-0.25% Avena Sativa Oat Leaf/Stem Extract 0.1-1% Benzoic acid 0.1-0.5% Caprylyl Glycol 0.2-0.5% Carbomer 0.10-0.25% Propylene glycol 0.1-10% scleroglucan gum 0.01-0.15% Sodium hydroxide 0.1-0.5% Uncaria Tomentosa Extract 0.1-3%

Claims (22)

Combination comprising an Uncaria Tomentosa liana extract and an oat seedling extract. Combination according to Claim 1, characterized in that the Uncaria Tomentosa liana extract is a hydroglycolic extract. Association according to one of Claims 1 or 2, characterized in that the oat seedling extract is an aqueous extract. Combination according to one of Claims 1 to 3, for its use in the prevention and/or treatment of neurogenic cutaneous inflammation. Combination according to one of Claims 1 to 3, for its use as modulator of nociceptive pathways. Combination for its use according to claim 4, characterized in that the neurogenic cutaneous inflammation comprises irritated skin and/or fragile skin. Combination according to one of Claims 1 to 3, for its use in the prevention and/or treatment of itching sensations and/or skin pain. Combination for its use according to claim 7, characterized in that the sensations of itching and/or skin pain are due to an inflammatory dermatosis. Combination for its use according to claim 7, characterized in that the sensations of itching and/or skin pain are due to a prick, a blow or a medical or surgical act. Combination according to one of claims 1 to 3, for its use in the prevention and/or treatment of inflammatory dermatoses, chosen in particular from atopic dermatitis, eczema, psoriasis, rosacea, lichen planus, prurigos, seborrheic dermatitis or acne. Cosmetic or dermatological composition comprising, as active principle, a combination according to any one of Claims 1 to 3, with at least one cosmetically or dermatologically acceptable excipient. Composition according to Claim 11, characterized in that it comprises 0.01 to 5%, in particular 0.05 to 3%, preferably 0.1 to 1% by weight of an oat seedling extract relative to the total weight of the composition. Composition according to either of Claims 11 and 12, characterized in that it comprises 0.01 to 10%, in particular 0.05 to 5%, preferably 0.1 to 3% by weight of an extract of Uncaria tomentosa vine relative to the total weight of the composition. Composition according to any one of Claims 11 to 13, characterized in that it is in a form suitable for topical application. Composition according to any one of Claims 11 to 14, characterized in that it is formulated in the form of a spray. Dermatological composition according to any one of Claims 11 to 15, for its use in the prevention and/or treatment of neurogenic cutaneous inflammation. Composition according to Claim 16, for its use in relieving irritated skin and/or fragile skin. Dermatological composition according to any one of Claims 11 to 15, for its use as a modulator of the nociceptive pathways. Dermatological composition according to any one of Claims 11 to 15, for its use in the prevention and/or treatment of itching sensations and/or skin pain. Dermatological composition according to Claim 19, for its use for relieving itching and/or skin pain due to an inflammatory dermatosis. Dermatological composition according to Claim 19, for its use for relieving itching and/or skin pain due to a bite, a blow or a medical or surgical procedure. Dermatological composition according to any one of Claims 11 to 15, for its use in the prevention and/or treatment of inflammatory dermatoses, chosen in particular from atopic dermatitis, eczema, psoriasis, rosacea, lichen planus, prurigos, seborrheic dermatitis or acne.