Anti-inflammatory composition comprising colloidal silver and plant extracts

Abstract

The invention relates to a composition for use as a medicament in the prophylaxis and / or treatment of inflammation, comprising at least silver in colloidal form, an extract of Sambucus nigra, an extract of Primulae flos cum calycibus and / or Hypericum perforatum extract, an extract of Pelargonium sidoides. In one embodiment, said composition is used in the prophylaxis and / or treatment of Staphylococcus aureus-induced inflammation.

Description

Description ANTI-INFLAMMATORY COMPOSITION COMPRISING COLLOIDAL SILVER AND PLANT EXTRACTS

[0001] The invention relates to a composition for use as a medicament in the prophylaxis and / or treatment of inflammation comprising at least silver in colloidal form, an extract of Sambucus Nigra, an extract of Hypericum perforatum, an extract of Pelargonium sidoides. According to one embodiment, said composition is used in the prophylaxis and / or treatment of inflammation induced by Staphylococcus aureus.

[0002] The invention relates to the field of prophylaxis and treatment of inflammations, in particular linked to Staphylococcus aureus. PREVIOUS ART

[0003] The therapeutic properties of silver were already known in ancient Greece: it was known that in families where silver cutlery was used for eating, infections were less frequent. Silver has important antimicrobial properties since the presence of one part in 100 million of elemental silver in solution is sufficient to obtain an effective antimicrobial action. It is also well known that the ions or free radicals of silver are an active antimicrobial agent.

[0004] To make silver soluble in water, it is necessary to use a colloidal ionic form (a suspension in water of extremely fine silver particles), which was first obtained in 1920 through a hydrolysis process in which two pure silver electrodes are used, immersed in demineralized or distilled water, to which a potential difference is applied.

[0005] Before the advent of antibiotics in 1938, colloidal silver was prescribed for a wide variety of illnesses and infections, having been proven effective against over 650 different pathogens.

[0006] Colloidal silver actually helps improve the functioning of the immune system because it acts as a catalyst, deactivating specific enzymes necessary for the metabolism of many bacterial, fungal and viral species.

[0007] This success is due to the fact that it is a safe antiseptic; in fact, when used in colloidal form, silver is absorbed very slowly by the tissues so as not to cause toxic effects, so it can be taken orally and is part of the preparations that can be taken daily by adults and children without the risk of any intolerance appearing, even if the use is prolonged over time.

[0008] Colloidal silver is primarily used as an antiseptic in dermatology for the treatment of certain types of lesions. It is also known for its use as a water purification agent and as a preservative in the cosmetics industry.

[0009] Colloidal silver, however, is not effective against all fungi, viruses, and bacteria.

[0010] Staphylococcus aureus is a major pathogen causing various bacterial skin infections (Liu et al., 2018; Tatiya-Aphiradee et al., 2019). This bacterium is the most frequently encountered strain of staphylococcus in human and veterinary pathology. It shares with the bacterium Escherichia coli the unfortunate privilege of being at the forefront rank of germs responsible for nosocomial infections. In France, A. aureus is also the leading bacteria responsible for food poisoning.

[0011] Inflammation is considered a reaction resulting from two conditions: a pathological state or a host defense against pathogens (Medzhitov, 2008; Gunalan et al., 2014; Greten, & Grivennikov, 2019; Agarwal, & Shanmugam, 2020). It is well known that prolonged inflammation can lead to the development of rheumatoid arthritis, inflammatory bowel disease, asthma, and pancreatitis (Mueller et al., 2010) as well as lead to a predisposition to cancer (Agarwal, & Shanmugam, 2020). An increase in the levels of cytokines, cytokine receptors, adhesion molecules, immunoregulatory factors, and several other mediators constitutes the key mechanism of inflammation (Gunalan et al., 2014). Because chronic inflammation can lead to irreversible consequences, many studies are focusing on the development of anti-inflammatory products.Unfortunately, many drugs available on the market are associated with unwanted side effects. It is well known that the IL-1 family is involved in acute and chronic inflammation (Kolb et al., 2001) and therefore plays an important role in regulating inflammatory processes (Sims and Smith, 2010). The IL-1 gene family is characterized by three components - IL-1α, IL-1β, and IL-1 receptor antagonist (IL-1RA) (Dinarello, 1997). IL-1β is released after proteolytic cleavage and is most likely involved in the inflammatory process (Kolb et al., 2001) because its overexpression and the subsequent inflammatory cascade can lead to the development of autoimmune disease (Pathak et al., 2011). Given the pathophysiological relevance of IL-ip, many studies have focused on the development of drugs and products targeting this interleukin (Peirô et al., 2017).To date, several drugs have been approved, such as anakinra, rilonacept, and canakinumab (Peirô et al., 2017).

[0012] Furthermore, IL-8 overexpression and upregulation have been reported to be linked to several cancers, including breast cancer (Singh et al., 2013). However, studies have revealed a significant increase in postmenopausal women with osteoporosis and bone loss (Al-Daghri et al., 2014). Thus, reducing this marker may provide significant advances in addressing these health issues.

[0013] There is therefore a continuing need for an alternative to existing anti-inflammatory compositions that is effective while limiting associated side effects. In particular, there is a continuing need for treatment and prophylactic treatment of inflammation, particularly related to Staphylococcus aureus infections.

[0014] Unexpectedly, the applicant unexpectedly demonstrated that the combination of colloidal silver with several plant extracts made it possible to obtain a composition effective in the prophylaxis and / or treatment of inflammations, in particular Staphylococcus aureus inflammations. Indeed, the applicant identified that the composition according to the invention had the capacity to reduce the production of inflammatory cytokines. DESCRIPTION

[0015] Thus, according to a first aspect, the invention relates to a composition for use as a medicament in the prophylaxis and / or treatment of inflammation including: - Silver in colloidal form; - An extract of Sambucus Nigra - An extract of Hypericum perforatum - An extract of pelargonium sidoides.

[0016] According to the invention, colloidal ionic silver is understood to mean a suspension of extremely fine silver particles in water.

[0017] Preferably, said silver in colloidal form has a particle size of between 0.1 and 30 nanometers.

[0018] Preferably, said composition for use according to the invention comprises: - Between 20 mg and 250 mg of silver in colloidal form per liter of composition.

[0019] By convention, it is generally considered that Img of silver is equivalent to Ippm in a 1 Liter solution, i.e. 20mg to 250mg per liter of solution.

[0020] Sambucus Nigra, or Black Elderberry, is a shrubby plant in the Caprifoliaceae family. Extracts from this plant can be derived from its flowers or fruits, and can be dry, aqueous, and / or alcoholic extracts.

[0021] Preferably, said composition for use according to the invention comprises: - Between 0.3 and 5% by weight of the composition of Sambucus Nigra Extract.

[0022] Hypericum perforatum or St. John's Wort, more commonly known as St. John's Wort, is a perennial herb of the Clusiaceae family. These extracts come from the plant or the flowering tops, which can be ground, optionally in water and / or alcohol.

[0023] Preferably, said composition for use according to the invention comprises: - Between 0.5 and 11% by weight of the composition of a Hypericum perforatum extract.

[0024] Pelargonium sidoides, or Umckaloabo, is a plant native to South Africa. Extracts of this plant can take the form of dry, aqueous, and / or alcoholic extracts of the roots or other parts of the plant.

[0025] Preferably, said composition for use according to the invention comprises: - Between 1 and 6% by weight of the composition of Pelargonium sidoides Extract.

[0026] By "treatment" is understood according to the invention the administration of the composition according to the invention to a patient having a pathology, in order to help him to cure it, to relieve his symptoms, in this case in the context of the present invention inflammation, preferably in connection with a 5. aureus infection.

[0027] By "prophylaxis" is meant according to the invention the implementation of the composition according to the invention to an individual or to a patient to prevent the occurrence or the spread of a pathology, in this case in the context of the present invention inflammation, preferably in connection with an S. aureus infection.

[0028] Inflammation is the body's immune response to some form of aggression. Inflammation can be acute or chronic. Signs Clinical signs of inflammation are pain (throbbing), redness, swelling (edema), a feeling of warmth, and functional impotence. Histologically, in acute forms, there are successive local vascular changes (vasodilation with slowing of circulation, increased permeability, and edema), followed by an influx of circulating leukocytes, first granulocytes, then monocytes with margination, adhesion to endothelial cells, diapedesis, phagocytosis of foreign substances and cellular and tissue debris, and possibly pus formation. The course of the inflammatory reaction is variable. In acute inflammation, after elimination of the causative agent, mononuclear phagocytes (monocytes, macrophages, histiocytes, etc.) ensure the cleaning of the inflammatory focus and we see either a "restitution ad integrum" without after-effects, or the replacement of the destroyed tissues by cicatricial fibrosis without functional restitution. In other cases, in the absence of elimination of the cause or due to the deficiency of certain defense mechanisms of the organism, the inflammation becomes chronic characterized by the formation of a generally mixed inflammatory infiltrate (granulocytes, histiocytes-macrophages, lymphocytes, even giant and epithelioid cells) with phenomena of neo-angiogenesis and especially processes of tissue remodeling (associating phenomena of destruction and reconstruction) with in particular a significant fibroblastic proliferation. The inflammatory reaction involves a large number of cell types (mononuclear and polymorphonuclear phagocytes, lymphocytes, platelets, but also tissue-specific cells, endothelial cells, etc.) and humoral mediators (complement, contact system, hemostasis protein), which are all targets for therapeutics. Finally, most inflammatory reactions induce a systemic response involving an increase in plasma levels of so-called acute-phase proteins (such as C-reactive protein, serum amyloid A protein, several a-1-globulins, certain complement components, fibrinogen, haptoglobin and a decrease in the concentrations of other proteins such as albumin, transferrin, fibronectin, apoprotein A1.The inflammatory response also involves interleukins, including the IL-1 family (IL-1α, IL-1β, and IL-1β receptor antagonist (IL-1RA) (Dinarello, 1997)), which plays an important role in regulating inflammatory processes (Sims and Smith, 2010). IL-8 is also an interleukin known to be involved in inflammation.

[0029] The composition for use according to the invention makes it possible to reduce the production of inflammatory cytokines, in particular IL-8, IP-10, IL-1 [3 and IL-6.

[0030] According to one embodiment, said composition for use according to the invention comprises: - Between 20 mg and 250 mg of silver in colloidal form per liter of composition.; - Between 0.3 and 5% by weight of the composition of Sambucus Nigra Extract - Between 0.5 and 11% by weight of the composition of a Hypericum perforatum extract - Between 1 and 6% by weight of the composition of Pelargonium sidoides Extract.

[0031] According to one embodiment, said composition for use according to the invention further comprises: - Silver in ionic form;

[0032] According to the invention, ionic silver is understood to mean silver whose particles have been dissolved in water, as opposed to colloidal silver where said particles are suspended in water.

[0033] According to one embodiment, said composition for use according to this latter embodiment comprises: - Between 20 mg and 250 mg of total silver per liter of composition, divided into i. Between 70 and 99.99% by total weight of silver, silver in colloidal form; ii. Between 0.01 and 30% by total weight of silver, silver in ionic form.

[0034] According to the invention, total silver is understood to mean all of the silver included in the composition according to the invention, whatever its form.

[0035] According to one embodiment, said composition for use comprises: - Between 20 mg and 250 mg of total silver per liter of composition, divided into i. Between 70 and 99.99% by total weight of silver, silver in colloidal form; ii. Between 0.01 and 30% by total weight of silver, silver in ionic form; - Between 0.3 and 5% by weight of the composition of Sambucus Nigra Extract - Between 0.5 and 11% by weight of the Hypericum perforatum extract composition - Between 1 and 6% by weight of the composition of Pelargonium sidoides Extract.

[0036] According to one embodiment, said composition for use according to the invention further comprises: - An Echinacea extract, and / or - Propolis and / or - An extract of Artemisia and / or - An Allium sativum extract and / or - An extract of Primulae flos cum calycibus.

[0037] Primulae flos cum calycibus, or Cowslip, is a perennial herbaceous plant of the Primulaceae family. These extracts are obtained by crushing the flowers and / or calyx of this plant, optionally in water and / or alcohol. These extracts can also be dry extracts.

[0038] Preferably, said composition for use according to the invention comprises: - Between 1 and 9% by weight of the composition of Primulae flos cum calycibus extract.

[0039] Echinacea, or coneflowers, refers to a genus of plants in the Asteraceae family. These extracts come in the form of dry, aqueous, and / or alcoholic extracts, produced from the root, the whole plant, or the aerial parts.

[0040] Preferably, said composition for use according to the invention comprises: - Between 0.01 and 8% by weight of the Echinacea extract composition.

[0041] Allium sativum, more commonly known as garlic, is a perennial plant. Extracts can be in the form of a dry, aqueous, and / or alcoholic extract, or an aged garlic extract.

[0042] Preferably, said composition for use according to the invention comprises: - Between 0.01 and 10% by weight of the Allium sativum extract composition.

[0043] Propolis is a product derived from plant resins and exudates, which can be secreted by plants or produced by bees from plant resin and wax. Since propolis depends on the plant species from which it is produced, standardized propolis is produced, often defined by their color. Preferably, yellow, green, or red propolis will be used here. Said propolis can be presented in the form of dry, purified, aqueous, and / or alcoholic extract.

[0044] Preferably, said composition for use according to the invention comprises: - Between 0.01 and 7% by weight of the propolis composition.

[0045] Artemisia or Mugwort is a genus of plant species comprising herbaceous plants, shrubs and bushes, with pinnate leaves. Preferably, the species used according to the invention is Artemisia annua. The latter is an aromatic branched herbaceous plant. Extracts from this plant can come from the whole plant or from the aerial parts, and can be dry, aqueous and / or alcoholic extracts.

[0046] Preferably, said composition for use according to the invention comprises: - Between 0.5 and 3% by weight of the composition of Artemisia extract.

[0047] Preferably, said composition for use according to the invention comprises: - Between 0.01 and 8% by weight of the composition of Echinacea extract, and / or - Between 0.01 and 7% by weight of the Propolis composition, and / or - Between 0.5 and 3% by weight of the composition of Artemisia extract, and / or - Between 0.01 and 10% by weight of the composition of Allium sativum extract and / or - Between 1 and 9% by weight of the Primulae flos cum calycibus extract composition.

[0048] Preferably according to the invention, said composition for use according to the invention comprises at least one other dermatologically and / or pharmaceutically acceptable agent.

[0049] According to one embodiment, said composition for use according to the invention is intended to be used as a medicament in the prophylaxis and / or treatment of inflammation induced by Staphylococcus aureus.

[0050] Staphylococcus aureus or golden staph is a Gram-positive bacterium characterized by rapidly increasing resistance to antibiotics (Tatiya-Aphiradee et al., 2019).

[0051] Preferably, said composition for use according to the invention can be administered orally, intravenously, subcutaneously, nasally, ophthalmically, auricularly, rectally, vaginally, respiratoryly, or by application to the skin.

[0052] Even more preferably, the oral route may take the form of a tablet, a syrup, a solution or an oral suspension, a capsule, preferably a tablet.

[0053] Even more preferably, the intravenous route may take the form of a solution.

[0054] Even more preferably, the subcutaneous route may take the form of a solution.

[0055] Preferably, administration is carried out by application to the skin.

[0056] Even more preferably, the route of application to the skin may take the form of an ointment, a cream, a patch, a liquid solution or a gel.

[0057] Even more preferably, the route of application to the skin takes the form of a cream, or a liquid solution.

[0058] Preferably, said composition for use according to the invention is administered by respiratory or nasal route, in the form of nasal drops, nasal spray, nasal powder, aerosol, for example compressed gas aerosols and / or nasal spray, or a nebulizer.

[0059] Advantageously, when the composition is suitable for nasal or respiratory administration, it can advantageously be for bronchopulmonary or sinus purposes.

[0060] Preferably, said composition for use according to the invention is administered by aerosol into the nasal passages.

[0061] The composition according to the present invention can be administered to a patient daily, once a day, twice a day, three times a day or even more times a day.

[0062] Preferably, the composition of the present invention is administered to a patient once daily.

[0063] The composition according to the invention may also comprise a physiologically acceptable medium, that is to say compatible with the skin or the different modes of administration envisaged.

[0064] According to one embodiment of the invention, said composition comprises, by weight of the composition: - Pharmaceutical grade purified water: qsp - 20 mg of Silver in total, consisting of 20% silver in ionic form and 80% silver in colloidal form, with an average particle size of 0.8nm; - 0.9% Sambucus Nigra extract; - 5% Hypericum perforatum extract; - 1.5% dry extract of Pelargonium sidoides; - 3% dry Echinacea extract; - 4% purified Propolis extract.

[0065] According to one embodiment of the invention, said composition comprises, by weight of the composition: - Pharmaceutical grade purified water: qsp - 20 mg of Silver in total at a rate of 20% silver in ionic form and 80% silver in colloidal form, with an average particle size of 0.8nm; - 0.9% Sambucus Nigra extract; - 5% dry extract Primulae flos cum calycibus; - 5% Hypericum perforatum extract; - 1.5% dry extract of Pelargonium sidoides; - 3% dry Echinacea extract; - 4% purified Propolis extract.

[0066] According to one embodiment of the invention, said composition comprises, by weight of the composition: - 20 mg of Silver in total, consisting of 20% silver in ionic form and 80% silver in colloidal form, with an average particle size of 0.8nm. - 0.9% Sambucus Nigra extract - 5% dry extract of Hypericum perforatum - 1.5% dry extract of Pelargonium sidoides. - 3% dry Echinacea extract - 4% purified Propolis extract.

[0067] According to a second aspect, the invention relates to a cosmetic or dermatological composition comprising: - Silver in colloidal form; - An extract of Sambucus Nigra - A Hypericum perforatum extract; - An extract of pelargonium sidoides.

[0068] Preferably, said cosmetic or dermatological composition according to the invention comprises: - Between 20 mg and 250 mg of silver in colloidal form per liter of composition.

[0069] Preferably, said cosmetic or dermatological composition according to the invention comprises: - Between 0.3 and 5% by weight of the composition of Sambucus Nigra Extract.

[0070] Preferably, said cosmetic or dermatological composition according to the invention comprises: - Between 0.5 and 11% by weight of the composition of an extract of Hypericum perforatum.

[0071] Preferably, said cosmetic or dermatological composition according to the invention comprises: - Between 1 and 6% by weight of the composition of Pelargonium sidoides Extract.

[0072] According to one embodiment, said cosmetic or dermatological composition according to the invention comprises: - Between 20 mg and 250 mg of silver in colloidal form per liter of composition.; - Between 0.3 and 5% by weight of the composition of Sambucus Nigra Extract; - Between 0.5 and 11% by weight of the composition of a Hypericum perforatum extract; - Between 1 and 6% by weight of the composition of Pelargonium sidoides Extract.

[0073] According to one embodiment, said cosmetic or dermatological composition according to the invention further comprises: - Silver in ionic form;

[0074] According to one embodiment, said cosmetic or dermatological composition according to this latter embodiment comprises: - Between 20 mg and 250 mg of total silver per liter of composition, divided into i. Between 70 and 99.99% by total weight of silver, silver in colloidal form; ii. Between 0.01 and 30% by total weight of silver, silver in ionic form.

[0075] According to one embodiment, said cosmetic or dermatological composition comprises: - Between 20 mg and 250 mg of total silver per liter of composition, divided into i. Between 70 and 99.99% by total weight of silver, silver in colloidal form; ii. Between 0.01 and 30% by total weight of silver, silver in ionic form; - Between 0.3 and 5% by weight of the composition of Sambucus Nigra Extract; - Between 0.5 and 11% by weight of the composition of Hypericum perforatum extract - Between 1 and 6% by weight of the composition of Pelargonium sidoides Extract.

[0076] According to one embodiment, said cosmetic or dermatological composition according to the invention further comprises: - An Echinacea extract, and / or - Propolis and / or - An extract of Artemisia and / or - An extract of Allium sativum and / or - An extract of Primulae flos cum calycibus.

[0077] Preferably, said cosmetic or dermatological composition according to the invention comprises: - Between 1 and 9% by weight of the composition of Primulae flos cum calycibus extract.

[0078] Preferably, said cosmetic or dermatological composition according to the invention comprises: - Between 0.01 and 8% by weight of the Echinacea extract composition.

[0079] Preferably, said cosmetic or dermatological composition according to the invention comprises: - Between 0.01 and 10% by weight of the composition of Allium sativum extract.

[0080] Preferably, said cosmetic or dermatological composition according to the invention understand : - Between 0.01 and 7% by weight of the propolis composition.

[0081] Preferably, said cosmetic or dermatological composition according to the invention comprises: - Between 0.5 and 3% by weight of the composition of Artemisia extract.

[0082] Preferably, said cosmetic or dermatological composition according to the invention comprises: - Between 0.01 and 8% by weight of the Echinacea extract composition, and / or - Between 0.01 and 7% by weight of the Propolis composition, and / or - Between 0.5 and 3% by weight of the composition of Artemisia extract, and / or - Between 0.01 and 10% by weight of the composition of Allium sativum extract and / or - Between 1 and 9% by weight of the Primulae flos cum calycibus extract composition.

[0083] According to one embodiment of the invention, said cosmetic or dermatological composition comprises, by weight of the composition: - Pharmaceutical grade purified water: qsp - 20 mg of Silver in total at a rate of 20% silver in ionic form and 80% silver in colloidal form, with an average particle size of 0.8nm; - 0.9% Sambucus Nigra extract - 5% Hypericum perforatum extract - 1.5% dry extract of Pelargonium sidoides; - 3% dry Echinacea extract; - 4% purified Propolis extract.

[0084] According to one embodiment of the invention, said cosmetic or dermatological composition comprises, by weight of the composition: - Pharmaceutical grade purified water: qsp - 20 mg of Silver in total at a rate of 20% silver in ionic form and 80% silver in colloidal form, with an average particle size of 0.8nm; - 0.9% Sambucus Nigra extract - 5% dry extract Primulae flos cum calycibus; - 5% Hypericum perforatum extract - 1.5% dry extract of Pelargonium sidoides; - 3% dry Echinacea extract; - 4% purified Propolis extract.

[0085] According to one embodiment of the invention, said cosmetic or dermatological composition comprises, by weight of the composition: - 20 mg of Silver in total, consisting of 20% silver in ionic form and 80% silver in colloidal form, with an average particle size of 0.8nm. - 0.9% Sambucus Nigra extract; - 5% Hypericum perforatum dry extract; - 1.5% dry extract of Pelargonium sidoides; - 3% dry Echinacea extract; - 4% purified Propolis extract.

[0086] By "non-therapeutic cosmetic or dermatological composition" is meant within the meaning of the invention an application not intended to treat a patient but a healthy individual. In fact, the cosmetic composition according to the invention does not act as a medicine for the treatment of diseases, but makes it possible to improve the superficial visual appearance of inflamed skin. Within the scope of the invention, the cosmetic composition makes it possible to reduce the visual signs of inflammation.

[0087] Preferably, said cosmetic or dermatological composition comprises at least one cosmetically or dermatologically acceptable excipient.

[0088] By "cosmetically or dermatologically acceptable" is meant according to the invention an excipient which is useful in the preparation of a cosmetic or dermatological composition, which is generally safe, non-toxic and neither biologically nor otherwise undesirable and which is acceptable for cosmetic or dermatological use, in particular for application to the skin.

[0089] According to the invention, the term "extract" means a preparation obtained from the plants mentioned. Preferably, said extracts are obtained by using a solvent.

[0090] By "dry extract" is meant an extract from which the solvent has been evaporated, and from which only the active ingredient(s) of the plant remain.

[0091] The cosmetic or dermatological compositions according to the invention can thus be presented 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, liquid solutions, creams or sticks with excipients allowing in particular, for some, penetration in order to improve the properties and accessibility of the active ingredients.

[0092] According to a third aspect, the invention relates to the non-therapeutic cosmetic or dermatological use in a healthy subject of a composition comprising: - Silver in colloidal form; - An extract of Sambucus Nigra - A Hypericum perforatum extract - An extract of pelargonium sidoides.

[0093] Preferably, said composition in this cosmetic or dermatological use according to the invention comprises: - Between 20 mg and 250 mg of silver in colloidal form per liter of composition.

[0094] Preferably, said composition in this cosmetic or dermatological use according to the invention comprises: - Between 0.3 and 5% by weight of the composition of Sambucus Nigra Extract.

[0095] Preferably, said composition in this cosmetic or dermatological use according to the invention comprises: - Between 0.5 and 11% by weight of the composition of a Hypericum perforatum extract.

[0096] Preferably, said composition in this cosmetic or dermatological use according to the invention comprises: - Between 1 and 6% by weight of the composition of Pelargonium sidoides Extract.

[0097] According to one embodiment, said composition in this cosmetic or dermatological use according to the invention comprises: - Between 20 mg and 250 mg of silver in colloidal form per liter of composition.; - Between 0.3 and 5% by weight of the composition of Sambucus Nigra Extract; - Between 0.5 and 11% by weight of the composition of a Hypericum perforatum extract; - Between 1 and 6% by weight of the composition of Pelargonium sidoides Extract.

[0098] According to one embodiment, said composition in this cosmetic or dermatological use according to the invention further comprises: - Silver in ionic form;

[0099] According to one embodiment, said composition in this cosmetic or dermatological use according to this latter embodiment comprises: - Between 20 mg and 250 mg of total silver per liter of composition, divided into i. Between 70 and 99.99% by total weight of silver, silver in colloidal form; ii. Between 0.01 and 30% by total weight of silver, silver in ionic form.

[0100] According to one embodiment, said composition in this cosmetic or dermatological use comprises: - Between 20 mg and 250 mg of total silver per liter of composition, divided into i. Between 70 and 99.99% by total weight of silver, silver in colloidal form; ii. Between 0.01 and 30% by total weight of silver, silver in ionic form; - Between 0.3 and 5% by weight of the composition of Sambucus Nigra Extract - Between 0.5 and 11% by weight of the Hypericum perforatum extract composition - Between 1 and 6% by weight of the composition of Pelargonium sidoides Extract.

[0101] According to one embodiment, said composition in this cosmetic or dermatological use according to the invention, further comprises: - An Echinacea extract, and / or - Propolis and / or - An extract of Artemisia and / or - An extract of Allium sativum and / or - An extract of Primulae flos cum calycibus

[0102] Preferably, said composition in this cosmetic or dermatological use according to the invention comprises: - Between 1 and 9% by weight of the composition of Primulae flos cum calycibus extract.

[0103] Preferably, said composition in this cosmetic or dermatological use according to the invention comprises: - Between 0.01 and 8% by weight of the Echinacea extract composition.

[0104] Preferably, said composition in this cosmetic or dermatological use according to the invention comprises: - Between 0.01 and 10% by weight of the composition of Allium sativum extract.

[0105] Preferably, said composition in this cosmetic or dermatological use according to the invention comprises: - Between 0.01 and 7% by weight of the propolis composition.

[0106] Preferably, said composition in this cosmetic or dermatological use according to the invention comprises: - Between 0.5 and 3% by weight of the composition of Artemisia extract.

[0107] Preferably, said composition in this cosmetic or dermatological use according to the invention comprises: - Between 0.01 and 8% by weight of the Echinacea extract composition, and / or - Between 0.01 and 7% by weight of the Propolis composition, and / or - Between 0.5 and 3% by weight of the composition of Artemisia extract, and / or - Between 0.01 and 10% by weight of the composition of Allium sativum extract and / or - Between 1 and 9% by weight of the Primulae flos cum calycibus extract composition.

[0108] According to one embodiment of the invention, this cosmetic use makes it possible to reduce the visual signs of inflammation.

[0109] By "reducing the visual signs of inflammation" is meant that in healthy subjects showing slight visual signs of inflammation, such as redness, the cosmetic composition according to the invention makes it possible to reduce this visibility. In this case, the cosmetic composition according to the invention acts only on the visible signs of inflammation.

[0110] According to one embodiment of the invention, this cosmetic use makes it possible to prevent and / or reduce the intensity of skin redness and / or lighten and / or even out the complexion and / or mask surface redness, in healthy subjects.

[0111] According to one embodiment of the invention, said composition in this cosmetic or dermatological use comprises, by weight of the composition: - Pharmaceutical grade purified water: qsp - 20 mg of Silver in total at a rate of 20% silver in ionic form and 80% silver in colloidal form, with an average particle size of 0.8nm; - 0.9% Sambucus Nigra extract - 5% Hypericum perforatum extract - 1.5% dry extract of Pelargonium sidoides; - 3% dry Echinacea extract - 4% purified Propolis extract.

[0112] According to one embodiment of the invention, said composition in this cosmetic or dermatological use comprises, by weight of the composition: - Pharmaceutical grade purified water: qsp - 20 mg of Silver in total at a rate of 20% silver in ionic form and 80% silver in colloidal form, with an average particle size of 0.8nm; - 0.9% Sambucus Nigra extract - 5% dry extract Primulae flos cum calycibus; - 5% Hypericum perforatum extract; - 1.5% dry extract of Pelargonium sidoides; - 3% dry Echinacea extract - 4% purified Propolis extract.

[0113] According to one embodiment of the invention, said composition in this cosmetic or dermatological use comprises, by weight of the composition: - 20 mg of Silver in total, consisting of 20% silver in ionic form and 80% silver in colloidal form, with an average particle size of 0.8nm. - 0.9% Sambucus Nigra extract; - 5% Hypericum perforatum dry extract; - 1.5% dry extract of Pelargonium sidoides; - 3% dry Echinacea extract - 4% purified Propolis extract.

[0114] According to a fourth aspect, the invention relates to a method of treating inflammation, preferably induced by S. aureus, comprising administering to a person in need thereof an effective amount of a composition according to the invention.

[0115] According to a fifth aspect, the invention relates to a process for preparing a cosmetic or dermatological composition according to the invention, comprising at least one step of mixing the compounds included in the composition.

[0116] In the description and in the following examples, unless otherwise indicated, the percentages are percentages by weight and the ranges of values ​​expressed in the form "between ... and ..." include the specified lower and upper limits. The examples below are presented for illustrative purposes and do not limit the scope of the invention.

[0117] The following examples illustrate the invention without limiting its scope. FIGURES

[0118] [Fig 1] is a histogram graph showing IL-8 concentrations (pg / ml) after various treatments: 1 - Composition according to Example 1 (as a liquid solution); 2 - Composition according to Example 1 (as a liquid solution) + S. aureus; 3 - Composition according to Example 1 as a cream; 4 - Composition according to Example 1 as a cream + A. aureus. Data were obtained from at least three independent experiments.

[0119] [Fig 2] is a histogram graph showing IP-10 concentrations (pg / ml) after different treatments: 1 - Composition according to example 1 (in the form of a liquid solution); 2 - Composition according to example 1 (in the form of a liquid solution) + 5. aureus; 3 - Composition according to Example 1 in the form of cream; 4 - Composition according to Example 1 in the form of cream + 5. aureus Data were obtained from at least three independent experiments.

[0120] [Fig 3] is a histogram graph showing IL-1 P concentrations (pg / ml) after various treatments: 1 - Composition according to Example 1 (as a liquid solution); 2 - Composition according to Example 1 (as a liquid solution) + . aureus 3 - Composition according to Example 1 in cream form; 4 - Composition according to Example 1 in cream form + S. aureus. Data were obtained from at least three independent experiments.

[0121] [Fig 4] is a histogram graph showing IL-6 concentrations (pg / ml) after various treatments: 1 - Composition according to Example 1 (as a liquid solution); 2 - Composition according to Example 1 (in the form of a liquid solution) + X aureus 3 - Composition according to Example 1 in the form of a cream; 4 - Composition according to Example 1 in the form of a cream + S. aureus. Data were obtained from at least three independent experiments. EXAMPLES:

[0122] Example 1: Example of composition:

[0123] The composition includes, per 100 mL of composition: - 20 mg of Silver in total, consisting of 20% silver in ionic form and 80% silver in colloidal form, with an average particle size of 0.8nm. - 0.9% Sambucus Nigra extract - 5% dry extract of Hypericum perforatum - 1.5% dry extract of Pelargonium sidoides. - 3% dry Echinacea extract - 4% purified Propolis extract.

[0124] Example 2: Anti-inflammatory activity of the composition of Example 1.

[0125] Materials and methods

[0126] The human epithelial cell line HT-29 was cultured as a monolayer in DMEM (Dulbecco's modified Eagle's medium, Gibco, UK), supplemented with 10% fetal bovine serum, at 37 °C and 5% CO2. In approximately 90% of the monolayers, cells were passaged by incubation with 0.25% trypsin solution and 10 mM EDTA for 10 minutes at 37 °C.

[0127] To determine the anti-inflammatory effect, eukaryotic cells were cultured in 24-well plates at a concentration of 2 * 10 5 cells / ml. The medium was changed every 2 days for a total of 14 days, promoting not only monolayer formation (3-4 days) but also maturation of cell receptors. The resulting monolayer was washed twice with Phosphate buffered saline (PB S).

[0128] DMEM medium (1 ml) containing different preparations was added to each well and incubated for 20 hours at 37 °C. The preparations were as follows - Control DMEM; - DMEM with Staphylococcus aureus IxlO 5 CFU / ml; - DMEM with 10% of the composition according to example 1 (in the form of liquid solution); - DMEM with 10% of the composition according to example 1 (in the form of liquid solution) and Staphylococcus aureus IxlO 5 CFU / ml; - DMEM with 10% of the composition according to example 1 in cream form; - DMEM with 10% of the composition according to example 1 in cream form and Staphylococcus aureus IxlO 5 CFU / ml.

[0129] After incubation, the cell-free supernatant was used to determine cytokine expression. IL-8, IP-10, EL-1P, and EL-6 were assessed by ELISA (enzyme-linked immunosorbent assays) according to the manufacturer's instructions (Diaclone, USA).

[0130] Results

[0131] These results indicate that Staphylococcus aureus increases the concentration of pro-inflammatory cytokines compared to untreated cell line samples - in DMEM medium. An approximately 3-fold increase was measured for IL-8 (Fig. 1) and IP-10 (Fig. 2). Approximately 2-fold higher levels were observed for IL-ip (Fig. 3). The lowest increase, approximately 1.5-fold, was obtained for IL-6 (Fig. 4). This result demonstrates that in these experiments, IL-8 and IP-10 are the most sensitive markers of Staphylococcus aureus-induced inflammation.

[0132] The data revealed no overexpression of IL-8 after treatment with both compositions according to the invention, in cream form or in liquid solution form (Fig. 1). No overexpression was measured after application of the products to cell lines in a state of inflammation caused by S. aureus. The measured levels were similar.

[0133] The next marker studied was IP-10. The data revealed that better protection expressed by the inhibition of IP-10 overexpression could be observed after application of the composition according to Example 1 when it is not in cream form (or in the form of a liquid solution), compared to the cream (Fig. 2).

[0134] The same was observed for the other marker studied - IL-1 - 60 times lower (Fig. 3). The composition according to Example 1 in the form of a cream reduced the induction of IL-1P by about 1.5 times.

[0135] With regard to IL-6, the most pronounced reduction was obtained after application of the composition according to Example 1 in cream form: approximately 9 times (Fig. 4). The reduction in IL-6 after application of the composition according to Example 1 was calculated to be approximately 6 times lower. Discussion

[0136] These results demonstrate that both preparations (the composition according to Example 1 in the form of a liquid solution and the composition according to Example 1 in the form of a cream) decrease the concentration of the four pro-inflammatory cytokines in both cases: control samples (DMEM); and cell lines in a state of inflammation caused by Staphylococcus aureus.

[0137] Based on the reported data, it can be concluded that the ability of the composition according to Example 1 in the form of a liquid solution to decrease the concentration of IL-8, IP-10, and IL-ip is greater compared to the effect of the composition according to Example 1 in cream form. On the other hand, the effect of the composition according to Example 1 in cream form was found to be more pronounced on IL-6 compared to the composition according to Example 1 which is not in cream form (in the form of a liquid solution). REFERENCES Agarwal, H., & Shanmugam, V. (2020). A review on anti-inflammatory activity of green synthesized zinc oxide nanoparticle: Mechanism-based approach. Bioorganic chemistry, 94, 103423. Al-Daghri, N.M., Yakout, S., Al-Shehri, E., Al-Fawaz, H., Aljohani, N., & Al-Saleh, Y. (2014). Inflammatory and bone turnover markers in relation to PTH and vitamin D status among Saudi postmenopausal women with and without osteoporosis. International journal of clinical and experimental medicine, 7(9), 2812. Dinarello, CA. Interleukin-1. Cytokine Growth Factor Rev 1997. 8:253-265. Greten, F. R., & Grivennikov, S. I. (2019). Inflammation and cancer: triggers, mechanisms, and consequences. Immunity, 51(T), 27-41. Gunalan, G., Vijayalakshmi, K., Saraswathy, A., Hopper, W., & Tamilvannan, T. (2014). Antiinflammatory activities of phytochemicals from Bauhinia variegata Linn, leaf: An in silico approach. J. chem. pharm, 6(9), 334-48. Kolb, M., Margetts, P. J., Anthony, D. C., Pitossi, F., & Gauldie, J. (2001). Transient expression of IL- Ip induces acute lung injury and chronic repair leading to pulmonary fibrosis. The Journal of clinical investigation, 707(12), 1529-1536. Liu, Q., Mazhar, M., & Miller, L. S. (2018). Immune and inflammatory reponses to Staphylococcus aureus skin infections. Current dermatology reports, 7(4), 338-349. Medzhitov, R. (2008). Origin and physiological roles of inflammation. Nature, 454(1203), 428- 435. Mueller, M., Hobiger, S., & Jungbauer, A. (2010). Anti-inflammatory activity of extracts from fruits, herbs and spices. Food chemistry, 122(4), 987-996. Pathak, S., Goldofsky, E., Vivas, E. X., Bonagura, V. R., & Vambutas, A. (2011). IL-ip is overexpressed and aberrantly regulated in corticosteroid nonresponders with autoimmune inner ear disease. The Journal of Immunology, 186(3), 1870-1879. Peiro, C., Lorenzo, O., Carraro, R., & Sânchez-Ferrer, C. F. (2017). IL-ip inhibition in cardiovascular complications associated to diabetes mellitus. Frontiers in pharmacology, 8, 363. Sims, J. E., and D. E. Smith. 2010. The IL-1 family: regulators of immunity. Nat. Rev. Immunol. 10: 89-102. Singh, J. K., Simôes, B. M., Howell, S. J., Farnie, G., & Clarke, R. B. (2013). Recent advances reveal IL-8 signaling as a potential key to targeting breast cancer stem cells. Breast Cancer Research, 15(4), 1-9. Tatiya-Aphiradee, N., Chatuphonprasert, W., & Jarukamjom, K. (2019). Anti-inflammatory effect of Garcinia mangostana Linn, pericarp extract in methicillin-resistant Staphylococcus aureus-induced superficial skin infection in mice. Biomedicine & Pharmacotherapy, 111, 705- 713.

Claims

Claims

1. A composition for use as a medicament in the prophylaxis and / or treatment of inflammation comprising: - Silver in colloidal form; - An extract of Sambucus Nigra; - An extract of Hypericum perforatum; - An extract of pelargonium sidoides.

2. Composition for use according to the preceding claim, characterized in that said silver in colloidal form has a particle size of between 0.1 and 30 nanometers.

3. A composition for use according to any preceding claim, comprising: - Between 20 mg and 250 mg of silver in colloidal form per liter of composition; - Between 0.3 and 5% by weight of the composition of Sambucus Nigra Extract; - Between 0.5 and 11% by weight of the composition of Hypericum perforatum extract; - Between 1 and 6% by weight of the composition of Pelargonium sidoides Extract.

4. A composition for use according to claims 1 and 2, further comprising: - Silver in ionic form;

5. Composition for use as a medicament according to the preceding claim, comprising: - Between 20 mg and 250 mg of total silver per liter of composition, divided into i. Between 70 and 99.99% by total weight of silver, silver in colloidal form; ii. Between 0.01 and 30% by total weight of silver, silver in ionic form. - Between 0.3 and 5% by weight of the composition of Sambucus Nigra Extract; - Between 0.5 and 11% by weight of the composition of Hypericum perforatum extract; - Between 1 and 6% by weight of the composition of Pelargonium sidoides Extract.

6. A composition for use according to any preceding claim, further comprising: - An extract of Echinacea, and / or - Propolis and / or - An extract of Artemisia and / or - An extract of Allium sativum and / or - An extract of Primulae flos cum calycibus.

7. Composition for use according to the preceding claim, comprising: - Between 0.01 and 8% by weight of the composition of Echinacea extract, and / or - Between 0.01 and 7% by weight of the Propolis composition, and / or - Between 0.5 and 3% by weight of the composition of Artemisia extract, and / or - Between 0.01 and 10% by weight of the composition of Allium sativum extract and / or - Between 1 and 9% by weight of the Primulae flos cum calycibus extract composition.

8. A composition for use according to any preceding claim, for use as a medicament in the prophylaxis and / or treatment of inflammation induced by Staphylococcus aureus.

9. A composition for use according to any one of the preceding claims, characterized in that it is in a form suitable for administration by application to the skin in the form of an ointment, cream, liquid solution, patch or gel, preferably a cream or liquid solution.

10. Non-therapeutic cosmetic use for reducing the visual signs of inflammation on the skin of a subject of a composition comprising: - Silver in colloidal form; - An extract of Sambucus Nigra; - An extract of Hypericum perforatum; - An extract of pelargonium sidoides.

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