Anti-inflammatory composition comprising colloidal silver and plant extract

Abstract

The invention relates to a composition used as a medicine for preventing and / or treating inflammation. The composition at least comprises silver in colloid form, sambucus nigra extract, primula calyx extract and / or hyperforin perforatum extract and South African geranium extract. According to one embodiment, the composition is used for preventing and / or treating inflammation induced by Staphylococcus aureus.

Description

Technical Field

[0001] The present invention relates to a composition for preventing and treating inflammation, comprising at least colloidal silver, an extract of Sambucus nigra, an extract of Hypericum perforatum, and an extract of Pelargonium sidoides. According to one embodiment, the composition is used to prevent and treat inflammation induced by Staphylococcus aureus.

[0002] The present invention relates to the prevention and treatment of inflammation, particularly inflammation induced by Staphylococcus aureus. Background Art

[0003] Knowledge of silver's therapeutic properties dates back to ancient Greece: it was known that households using silver cutlery were less susceptible to infection. Silver possesses numerous antimicrobial properties, with a solution containing only one part of elemental silver in 100 million parts being effective. Silver ions and free radicals are known to act as active antimicrobial agents.

[0004] To make silver soluble in water, it is necessary to use the colloidal ion form (extremely fine silver particles suspended in water), which was first produced in 1920 by hydrolysis, using two pure silver electrodes immersed in demineralized or distilled water and applying a voltage difference across them.

[0005] Before the advent of antibiotics in 1938, colloidal silver obtained using this method was used to treat a wide range of diseases and infections: in fact, it has been shown to be effective against more than 650 different pathogens.

[0006] Colloidal silver boosts the immune system by acting as a catalyst by inactivating specific enzymes required for the metabolism of various bacteria, fungi, and viruses.

[0007] Colloidal silver's success is due to its safety as a disinfectant. When used in colloidal form, silver is absorbed very slowly by tissues, preventing any toxic effects. Therefore, colloidal silver can be taken orally or in formulations that can be taken daily by adults and children, even over long periods of time, without the risk of intolerance.

[0008] Colloidal silver is primarily used as a disinfectant in dermatology to treat certain lesions. It is also known in the cosmetics industry for its use as a water purifier and preservative.

[0009] However, colloidal silver is not effective against all fungi, viruses, and bacteria.

[0010] Staphylococcus aureus is a major pathogen causing a variety of bacterial skin infections (Liu et al., 2018; Tatiya-Aphiradee et al., 2019). This bacterium is the best-known strain of Staphylococcus in both human and veterinary medicine. Along with Escherichia coli, it is a well-known leading cause of healthcare-associated infections. In France, S. aureus is also a leading cause of food poisoning.

[0011] Inflammation is a response triggered by two conditions: a pathological state or a host defense response against pathogens (Medzhitov, 2008; Gunalan et al., 2014; Greten & Grivennikov, 2019; Agarwal & Shanmugam, 2020). It is well known that long-term inflammation can lead to the onset of rheumatoid arthritis, inflammatory bowel disease, asthma, and pancreatitis (Mueller et al., 2010) and increase the risk of cancer (Agarwal & Shanmugam, 2020). Increased levels of cytokines, cytokine receptors, adhesion molecules, immunomodulatory factors, and many other mediators are key mechanisms of inflammation (Gunalan et al., 2014). Because chronic inflammation can lead to permanent effects, much research has focused on developing anti-inflammatory products. Unfortunately, many commercially available drugs have side effects. The IL-1 family of proteins is known to be involved in both acute and chronic inflammation (Kolb et al., 2001), and therefore plays a crucial role in controlling inflammatory processes (Sims et al., 2010). The IL-1 gene family consists of three components—IL-1α, IL-1β, and IL-1 receptor antagonist (IL-1RA) (Dinarello, 1997). IL-1β, released after proteolysis, is likely involved in inflammatory processes (Kolb et al., 2001), as its overexpression and subsequent inflammatory cascade contribute to the development of autoimmune diseases (Pa-thak et al., 2011). Given the physiopathological relevance of IL-1β, much research has focused on developing drugs and products targeting this interleukin (Peiró et al., 2017). To date, several drugs have been approved. These include anakinra, rilonacept, and canakinumab (Peiró et al., 2017).

[0012] Furthermore, overexpression and upregulation of IL-8 have been reported to be associated with many cancers, including breast cancer (Singh et al., 2013). However, studies have shown that postmenopausal women experience a significant increase in osteoporosis and bone loss (Al-Daghri et al., 2014). Therefore, reducing IL-8 expression could significantly improve these health issues.

[0013] Currently, no effective alternative to existing anti-inflammatory compositions has been found that reduces the associated side effects. In particular, there remains a need for preventative inflammatory treatments, particularly those associated with infections caused by Staphylococcus aureus.

[0014] Unexpectedly, the applicants have demonstrated in an unexpected manner that the combination of colloidal silver and several plant extracts produces a composition that is effective in preventing and / or treating inflammation, particularly inflammation induced by Staphylococcus aureus. In fact, the applicants have discovered that the composition of the present invention can reduce the production of inflammatory cytokines. Summary of the Invention

[0015] Therefore, according to a first aspect, the present invention relates to a composition for use as a medicament for preventing and / or treating inflammation, comprising:

[0016] -Silver in colloidal form;

[0017] - Sambucus Nigra extract;

[0018] - Hypericum perforatum extract;

[0019] -Pelargonium sidoides extract.

[0020] According to the present invention, ionic colloidal silver refers to very fine silver particles suspended in water.

[0021] Preferably, the particle size of the colloidal silver is 0.1-30 nm.

[0022] Preferably, the composition for use in the present invention comprises:

[0023] - The content of silver in colloidal form is between 20 mg and 250 mg per liter of the composition.

[0024] By convention, it is generally considered that 1 mg of silver in 1 liter of solution is equal to 1 ppm, that is, 20 mg-250 mg per liter of solution.

[0025] Sambucus nigra, also known as the pale black elderberry, is a shrub of the Caprifoliaceae family. Plant dry extracts, plant water extracts, and / or plant ethanol extracts can be extracted from its flowers or fruits.

[0026] Preferably, the composition for use in the present invention comprises:

[0027] - 0.3% to 5% by weight of an elderberry extract component.

[0028] Hypericum perforatum, also known as St. John's wort, is a perennial herb in the family Clusiceae. The extract is derived from the plant or flower tops, which may be optionally crushed in water and / or ethanol.

[0029] Preferably, the composition used in the present invention comprises:

[0030] - 0.5% to 11% by weight of a Hypericum perforatum extract component;

[0031] South African geranium, also known as Umckaloabo, is a plant native to South Africa. Extracts of this plant can be obtained in the form of dry, aqueous, and / or ethanolic extracts, derived from the roots or other plant parts.

[0032] Preferably, the composition for use in the present invention comprises:

[0033] - 1% to 6% by weight of a pelargonium extract component;

[0034] According to the present invention, "treatment" refers to the administration of a composition.

[0035] According to the present invention, in patients suffering from health conditions, in order to assist them in healing, relieving symptoms, inflammation (in this particular case of the present invention), preferably associated with infection induced by Staphylococcus aureus.

[0036] According to the present invention, "prevention" refers to the administration of the composition.

[0037] According to the present invention, it is used to prevent the onset or spread of a health condition in an individual or patient, in the specific case of the present invention said health condition is inflammation, preferably associated with an infection induced by Staphylococcus aureus.

[0038] "Inflammation" is the body's defensive response to an attack. Inflammation can be acute or chronic. The clinical symptoms of inflammation are pain (pulsating), redness, swelling (edema), fever and functional impotence. Histologically, in the acute form, there is a series of local vascular changes (vasodilation with slowed blood circulation, increased permeability and edema), followed by a surge in circulating leukocytes (initially granulocytes, then marginalized monocytes), adhesion to endothelial cells, hemodialysis, phagocytosis of foreign matter and cell and tissue debris, and possible formation of pus. The development of the inflammatory response is variable. In acute inflammation, after the elimination of the pathogen, mononuclear phagocytes (monocytes, macrophages, histiocytes, etc.) clean the site of inflammation, and either "restoration of integrity" occurs without any sequelae, or the destroyed tissue is replaced by scar fibrosis without functional recovery. In other cases, if the underlying cause is not eliminated or due to the failure of certain body defense mechanisms, inflammation becomes chronic, characterized by the formation of a usually mixed inflammatory infiltrate (granulocytes, histiocyte-macrophages, lymphocytes, and even giant cells and epithelioid cells), accompanied by neoangiogenesis, and especially tissue-changing processes (combined destruction and reconstruction), especially a marked fibroblast proliferation.

[0039] The inflammatory response involves all therapeutic targets, numerous cell types (mononuclear and multinuclear phagocytes, lymphocytes, platelets, as well as tissue cells and endothelial cells) and humoral mediators (complement, contact system, hemostatic proteins). Finally, most inflammatory responses induce systemic responses, including elevated plasma protein concentrations during the acute phase (e.g., C-reactive protein, serum amyloid A, several α-1-globulins, certain complement components, fibrinogen, haptoglobin), and decreased concentrations of other proteins, such as albumin, transferrin, fibronectin, and apolipoprotein A-1. Interleukins, including the IL-1 family (IL-1α, IL-1β, and IL-1 receptor antagonist (IL-1RA) (Dinarello, 1997), also participate in the inflammatory response and play an important role in controlling the inflammatory process (Sims et Smith, 2010). IL-8 is also an interleukin known to be involved in inflammation.

[0040] The composition used in the present invention reduces the production of inflammatory cytokines, particularly IL-8, IP-10, IL-1β and IL-6.

[0041] According to one embodiment, the composition for use according to the invention comprises:

[0042] - 20 mg to 250 mg of silver in colloidal form per liter of composition;

[0043] - 0.3% to 5% by weight of an elderberry extract component;

[0044] - 0.5% to 11% by weight of a Hypericum perforatum extract component;

[0045] - 1% to 6% by weight of a pelargonium officinale extract component.

[0046] According to one embodiment, the composition for use according to the invention further comprises:

[0047] -Silver in ionic form;

[0048] According to the present invention, ionic silver refers to silver whose particles have been dissolved in water, rather than colloidal silver in which the particles are suspended in water.

[0049] According to one embodiment, the composition used according to the latter embodiment comprises:

[0050] - The total silver content per liter of the composition is 20mg-250mg, distributed in

[0051] i. 70% to 99.99% by weight of silver in colloidal form;

[0052] ii. 0.01% to 30% by weight of silver, in ionic form;

[0053] According to the present invention, the total silver content refers to all silver contained in the composition of the present invention, regardless of its form.

[0054] According to one embodiment, the use composition comprises:

[0055] - the total silver content per liter of the composition is between 20 mg and 250 mg;

[0056] i. 70% to 99.99% by weight of silver in colloidal form;

[0057] ii. 0.01% to 30% by weight of silver, in ionic form;

[0058] - 0.3% to 5% by weight of an elderberry extract component;

[0059] - 0.5% to 11% by weight of a Hypericum perforatum extract component;

[0060] - 1% to 6% by weight of a pelargonium officinale extract component.

[0061] According to one embodiment, the composition for use according to the invention further comprises:

[0062] - Echinacea extract, and / or

[0063] - Propolis and / or

[0064] - Artemisia extract and / or

[0065] - Garlic (Allium sativum) extract and / or

[0066] -Primulaeflos cum calycibus extract.

[0067] Primula calyx, also known as yellow cowslip, is a perennial herb in the Primulaceae family. The extract is derived from the crushed flowers and / or calyx, optionally in water and / or ethanol. These extracts can also be dried extracts.

[0068] Preferably, the composition for use in the present invention comprises:

[0069] - 1% to 9% by weight of a Primula calyx extract component.

[0070] Echinacea is a genus of plants in the family Asteraceae. The extract is a dry extract, an aqueous extract and / or an ethanol extract from the root, the whole plant or the above-ground plant part.

[0071] Preferably, the composition for use in the present invention comprises:

[0072] - 0.01% to 8% by weight of Echinacea extract components.

[0073] Garlic is a perennial plant commonly known as "garlic".

[0074] The extracts may be in dry, aqueous and / or ethanolic form, or in the form of aged garlic extracts.

[0075] Preferably, the composition for use in the present invention comprises:

[0076] - 0.01% to 10% by weight of garlic extract components.

[0077] "Propolis" is a product derived from plant resins and exudates, which can be secreted by plants or produced by bees from plant resins and waxes. Because propolis depends on the plant species it produces, the production of standardized propolis is usually defined by its color. Preferably, yellow, green or red propolis is used. Described propolis can exist in the form of drying, purification, water and / or ethanol extracts.

[0078] Preferably, the composition for use in the present invention comprises:

[0079] - 0.01% to 7% by weight of propolis component.

[0080] Artemisia, also known as mugwort, is a genus of plants consisting of herbs and shrubs with pinnate leaves. Preferably, the species used in accordance with the present invention is Artemisia annua. It is an aromatic, branched herb. Extracts of this plant can be obtained from the whole plant or its aerial parts and can be dry extracts, aqueous extracts, and / or ethanol extracts.

[0081] Preferably, the composition for use in the present invention comprises:

[0082] - 0.5% to 3% by weight of an Artemisia extract component;

[0083] Preferably, the composition for use in the present invention comprises:

[0084] - 0.01% to 8% by weight of Echinacea extract components, and / or

[0085] - 0.01% to 7% by weight of a propolis composition, and / or

[0086] - 0.5w% to 3w% by weight of an Artemisia extract component, and / or

[0087] - 0.01% to 10% by weight of garlic extract components, and / or

[0088] - 1% to 9% by weight of a Primula calyx extract component.

[0089] According to the present invention, preferably, the composition for use according to the present invention comprises at least one other dermatologically and / or pharmaceutically acceptable agent.

[0090] According to one embodiment, the composition for use in the present invention is intended for use as a medicament for preventing and / or treating Staphylococcus aureus-induced inflammation.

[0091] Staphylococcus aureus is a Gram-positive bacterium characterized by a rapidly increasing resistance to antibiotics (Tatiya-Aphiradee et al., 2019).

[0092] Preferably, the composition for use in the present invention can be administered orally, intravenously, subcutaneously, nasally, ophthalmically, otically, rectally, vaginally, or by respiratory route, or can be applied to the skin.

[0093] Even more preferably, the oral route may be in the form of tablets, syrups, drinkable solutions or suspensions or capsules, preferably tablets.

[0094] Even more preferably, the intravenous route may be a solution.

[0095] Even more preferably, the subcutaneous injection route may be a solution.

[0096] Preferably, administration is by topical application.

[0097] Even more preferably, the topical application route may be an ointment, cream, patch, liquid solution or gel.

[0098] Even more preferably, the topical route of application is a cream or a liquid solution.

[0099] Preferably, the composition for use in the present invention is administered by the respiratory or nasal route, such as nasal drops, nasal sprays, nasal powder formulations, sprays, for example compressed gas nasal sprays or nebulizers.

[0100] Advantageously, when the composition is adapted for nasal or respiratory administration, it may be advantageously used for bronchopulmonary or sinus purposes.

[0101] Preferably, the composition for use in the present invention is administered by nasal spray.

[0102] The compositions of the present invention may be administered to the patient daily, once a day, twice a day, three times a day, or even more times a day.

[0103] Preferably, the composition of the present invention is administered once a day.

[0104] The compositions of the present invention may also comprise a physiologically acceptable medium, ie, for simultaneous use with the skin or other contemplated modes of administration.

[0105] According to one embodiment of the present invention, the composition comprises, by weight of the composition:

[0106] -Purified water for pharmaceutical use: appropriate amount (qs)

[0107] - 20mg total silver, up to 20% ionic silver and 80% colloidal silver, with an average particle size of 0.8nm; - 0.9% Sambucus nigra extract;

[0108] -5% Hypericum perforatum extract;

[0109] -1.5% South African geranium dry extract;

[0110] -3% Echinacea dry extract;

[0111] -4% purified propolis extract.

[0112] According to one embodiment of the present invention, the composition comprises, by weight of the composition:

[0113] -Purified water for pharmaceutical use: qs

[0114] - 20mg total silver, up to 20% ionic silver and 80% colloidal silver, with an average particle size of 0.8nm; - 0.9% Sambucus nigra extract;

[0115] -5% dry extract of Primula calyx;

[0116] -5% Hypericum perforatum extract;

[0117] -1.5% South African geranium dry extract;

[0118] -3% Echinacea dry extract;

[0119] -4% purified propolis extract.

[0120] According to one embodiment of the present invention, the composition comprises, by weight of the composition:

[0121] - 20mg total silver, up to 20% ionic silver and 80% colloidal silver, with an average particle size of 0.8nm. - 0.9% Sambucus nigra extract.

[0122] -5% Hypericum perforatum dry extract.

[0123] -1.5% South African geranium dry extract.

[0124] -3% Echinacea dry extract.

[0125] -4% purified propolis extract.

[0126] According to a second aspect, the present invention relates to a cosmetic or dermatological composition comprising:

[0127] -Silver in colloidal form;

[0128] - Sambucus nigra extract;

[0129] - Hypericum perforatum extract;

[0130] - South African geranium extract.

[0131] Preferably, the cosmetic or dermatological composition according to the invention comprises:

[0132] - Contains 20mg-250mg of silver in colloidal form per liter of composition.

[0133] Preferably, the cosmetic or dermatological composition according to the invention comprises:

[0134] - 0.3% to 5% by weight of an elderberry extract component.

[0135] Preferably, the cosmetic or dermatological composition according to the invention comprises:

[0136] - 0.5%-11% by weight of Hypericum perforatum extract.

[0137] Preferably, the cosmetic or dermatological composition according to the invention comprises:

[0138] - 1% to 6% by weight of a pelargonium officinale extract component.

[0139] According to one embodiment, the cosmetic or dermatological composition according to the invention comprises:

[0140] - 20 mg to 250 mg of colloidal silver per liter of composition;

[0141] - 0.3% to 5% by weight of an elderberry extract component;

[0142] - 0.5% to 11% by weight of a Hypericum perforatum extract component;

[0143] - 1% to 6% by weight of a pelargonium officinale extract component.

[0144] According to one embodiment, the cosmetic or dermatological composition according to the invention further comprises:

[0145] -Silver in ionic form;

[0146] According to one embodiment, the cosmetic or dermatological composition according to the latter embodiment comprises:

[0147] - The total silver content per liter of the composition is 20mg-250mg, distributed in

[0148] i. 70% to 99.99% by weight of silver in colloidal form;

[0149] ii. 0.01% to 30% by weight of silver, in ionic form;

[0150] According to one embodiment, the cosmetic or dermatological composition comprises:

[0151] - The total silver content per liter of the composition is 20mg-250mg, distributed in

[0152] i. 70% to 99.99% by weight of silver in colloidal form;

[0153] ii. 0.01% to 30% by weight of silver, in ionic form;

[0154] - 0.3% to 5% by weight of an elderberry extract component;

[0155] - 0.5% to 11% by weight of a Hypericum perforatum extract component;

[0156] - 1% to 6% by weight of a pelargonium officinale extract component.

[0157] According to one embodiment, the cosmetic or dermatological composition according to the invention further comprises:

[0158] - Echinacea extract, and / or

[0159] - Propolis and / or

[0160] - Artemisia extract and / or

[0161] - garlic extract and / or

[0162] -Primula calyx extract.

[0163] Preferably, the cosmetic or dermatological composition according to the invention comprises:

[0164] - 1% to 9% by weight of a Primula calyx extract component.

[0165] Preferably, the cosmetic or dermatological composition according to the invention comprises:

[0166] - 0.01% to 8% by weight of Echinacea extract components.

[0167] Preferably, the cosmetic or dermatological composition according to the invention comprises:

[0168] - 0.01% to 10% by weight of garlic extract components.

[0169] Preferably, the cosmetic or dermatological composition according to the invention comprises:

[0170] - 0.01% to 7% by weight of propolis component.

[0171] Preferably, the cosmetic or dermatological composition according to the invention comprises:

[0172] - 0.5% to 3% by weight of Artemisia extract components.

[0173] Preferably, the cosmetic or dermatological composition according to the invention comprises:

[0174] - 0.01% to 8% by weight of Echinacea extract components, and / or

[0175] - 0.01% to 7% by weight of a propolis component, and / or

[0176] - 0.5% to 3% by weight of an Artemisia extract component, and / or

[0177] - 0.01% to 10% by weight of garlic extract components, and / or

[0178] - 1% to 9% by weight of a Primula calyx extract component.

[0179] According to one embodiment of the invention, the cosmetic or dermatological composition comprises, by weight of the composition:

[0180] -Purified water for pharmaceutical use: qs

[0181] - 20mg total silver, up to 20% ionic silver and 80% colloidal silver, with an average particle size of 0.8nm;

[0182] -0.9% Sambucus nigra extract;

[0183] -5% Hypericum perforatum extract;

[0184] -1.5% South African geranium dry extract;

[0185] -3% Echinacea dry extract;

[0186] -4% purified propolis extract.

[0187] According to one embodiment of the invention, the cosmetic or dermatological composition comprises, by weight of the composition:

[0188] -Purified water for pharmaceutical use: qs

[0189] - 20mg total silver, up to 20% ionic silver and 80% colloidal silver, with an average particle size of 0.8nm;

[0190] -0.9% Sambucus nigra extract;

[0191] -5% dry extract of Primula calyx;

[0192] -5% Hypericum perforatum dry extract;

[0193] -1.5% South African geranium dry extract;

[0194] -3% Echinacea dry extract;

[0195] -4% purified propolis extract.

[0196] According to one embodiment of the invention, the cosmetic or dermatological composition comprises, by weight of the composition:

[0197] - 20mg silver in total, up to 20% ionic silver and 80% colloidal silver, with an average particle size of 0.8nm.

[0198] -0.9% Sambucus nigra extract;

[0199] -5% Hypericum perforatum dry extract;

[0200] -1.5% South African geranium dry extract;

[0201] -3% Echinacea dry extract;

[0202] -4% purified propolis extract.

[0203] Within the meaning of the present invention, a "non-therapeutic cosmetic or dermatological composition" is one that is not intended to treat a patient but is intended for use on healthy individuals. In fact, the cosmetic composition according to the invention does not act as a medicament for treating a disease, it improves the superficial visual appearance of inflamed skin.

[0204] Within the scope of the present invention, the cosmetic composition reduces the visual symptoms of inflammation.

[0205] Preferably, the cosmetic or dermatological composition comprises at least one cosmetically or dermatologically acceptable excipient.

[0206] According to the present invention, "cosmetically or dermatologically acceptable" refers to excipients that can be used to prepare cosmetic or dermatological compositions, which are generally safe, non-toxic, and not biologically or otherwise adverse, and which can be used for cosmetic and dermatological uses, including topical applications.

[0207] According to the present invention, "extract" refers to a preparation extracted from the listed plants. Preferably, the extract is obtained by using a solvent.

[0208] "Dry extract" refers to an extract from which the solvent has evaporated, leaving behind the active ingredients of the plant.

[0209] The cosmetic or dermatological compositions according to the invention may be in the conventionally known forms for topical application, i.e. emulsions, shampoos, balms, foams, gels, dispersions, lotions, sprays, serums, masks, liquid solutions, creams or sticks containing excipients, some of which are particularly penetrating in order to improve the properties and accessibility of the active ingredient.

[0210] According to a third aspect, the present invention relates to the non-therapeutic cosmetic or dermatological use in healthy subjects of a composition comprising:

[0211] -Silver in colloidal form;

[0212] - Sambucus nigra extract;

[0213] - Hypericum perforatum extract;

[0214] - South African geranium extract.

[0215] Preferably, the composition for the cosmetic or dermatological use according to the invention comprises:

[0216] - Contains 20mg-250mg of colloidal silver per liter of composition.

[0217] Preferably, the composition for the cosmetic or dermatological use according to the invention comprises:

[0218] - 0.3% to 5% by weight of an elderberry extract component.

[0219] Preferably, the composition for the cosmetic or dermatological use according to the invention comprises:

[0220] - 0.5%-11% by weight of Hypericum perforatum extract.

[0221] Preferably, the composition for the cosmetic or dermatological use according to the invention comprises:

[0222] - 1% to 6% by weight of a pelargonium officinale extract component.

[0223] According to one embodiment, the composition for cosmetic or dermatological use according to the invention comprises:

[0224] - 20 mg to 250 mg of colloidal silver per liter of composition;

[0225] - 0.3% to 5% by weight of an elderberry extract component;

[0226] - 0.5% to 11% by weight of a Hypericum perforatum extract component;

[0227] - 1% to 6% by weight of a pelargonium officinale extract component.

[0228] According to one embodiment, the composition for cosmetic or dermatological use according to the invention further comprises:

[0229] -Silver in ionic form;

[0230] According to one embodiment, the composition for cosmetic or dermatological use according to the latter embodiment comprises:

[0231] - The total silver content per liter of the composition is 20mg-250mg, distributed in

[0232] i. 70% to 99.99% by weight of silver in colloidal form;

[0233] ii. 0.01% to 30% by weight of silver, in ionic form;

[0234] According to one embodiment, the composition for said cosmetic or dermatological use comprises:

[0235] - The total silver content per liter of the composition is 20mg-250mg, distributed in

[0236] i. 70% to 99.99% by weight of silver in colloidal form;

[0237] ii. 0.01% to 30% by weight of silver, in ionic form;

[0238] - 0.3% to 5% by weight of an elderberry extract component;

[0239] - 0.5% to 11% by weight of a Hypericum perforatum extract component;

[0240] - 1% to 6% by weight of a pelargonium officinale extract component.

[0241] According to one embodiment, the composition for cosmetic or dermatological use according to the invention further comprises:

[0242] - Echinacea extract, and / or

[0243] - Propolis and / or

[0244] - Artemisia extract and / or

[0245] - garlic extract and / or

[0246] -Primula calyx extract.

[0247] Preferably, the composition for the cosmetic or dermatological use according to the invention comprises:

[0248] - 1% to 9% by weight of a Primula calyx extract component.

[0249] Preferably, the composition for the cosmetic or dermatological use according to the invention comprises:

[0250] - 0.01% to 8% by weight of Echinacea extract components.

[0251] Preferably, the composition for the cosmetic or dermatological use according to the invention comprises:

[0252] - 0.01% to 10% by weight of garlic extract components.

[0253] Preferably, the composition for the cosmetic or dermatological use according to the invention comprises:

[0254] - 0.01% to 7% by weight of propolis component.

[0255] Preferably, the composition for the cosmetic or dermatological use according to the invention comprises:

[0256] - 0.5% to 3% by weight of Artemisia extract components.

[0257] Preferably, the composition for the cosmetic or dermatological use according to the invention comprises:

[0258] - 0.01% to 8% by weight of Echinacea extract components, and / or

[0259] - 0.01% to 7% by weight of a propolis component, and / or

[0260] - 0.5% to 3% by weight of Artemisia extract components, and / or

[0261] - 0.01% to 10% by weight of garlic extract components, and / or

[0262] - 1% to 9% by weight of a Primula calyx extract component.

[0263] According to one embodiment of the invention, the cosmetic use reduces visual symptoms of inflammation.

[0264] "Reducing visual symptoms of inflammation" means that in healthy subjects with mild visual symptoms of inflammation (such as redness), the cosmetic composition of the present invention reduces this visibility. In this case, the cosmetic composition according to the present invention only acts on visible signs of inflammation.

[0265] According to one embodiment of the present invention, in healthy subjects, the use of the cosmetic can prevent and / or reduce the intensity of skin redness and / or brighten and / or harmonize skin tone and / or hide redness on the skin surface.

[0266] According to one embodiment of the invention, the composition for cosmetic or dermatological use comprises, by weight of the composition:

[0267] -Purified water for pharmaceutical use: qs

[0268] - 20mg total silver, up to 20% ionic silver and 80% colloidal silver, with an average particle size of 0.8nm;

[0269] -0.9% Sambucus nigra extract;

[0270] -5% Hypericum perforatum extract;

[0271] -1.5% South African geranium dry extract;

[0272] -3% Echinacea dry extract;

[0273] -4% purified propolis extract.

[0274] According to one embodiment of the invention, the composition for cosmetic or dermatological use comprises, by weight of the composition:

[0275] -Purified water for pharmaceutical use: qs

[0276] - 20mg total silver, up to 20% ionic silver and 80% colloidal silver, with an average particle size of 0.8nm;

[0277] -0.9% Sambucus nigra extract;

[0278] -5% dry extract of Primula calyx;

[0279] -5% Hypericum perforatum dry extract;

[0280] -1.5% South African geranium dry extract;

[0281] -3% Echinacea dry extract;

[0282] -4% purified propolis extract.

[0283] According to one embodiment of the invention, the composition for cosmetic or dermatological use comprises, by weight of the composition:

[0284] - A total of 20mg of silver, up to 20% ionic silver and 80% colloidal silver, with an average particle size of 0.8nm.

[0285] -0.9% Sambucus nigra extract;

[0286] -5% Hypericum perforatum dry extract;

[0287] -1.5% South African geranium dry extract;

[0288] -3% Echinacea dry extract;

[0289] -4% purified propolis extract.

[0290] According to a fourth aspect, the present invention relates to a method for treating inflammation, preferably induced by Staphylococcus aureus, comprising administering to a person in need thereof an effective amount of a composition of the present invention.

[0291] According to a fifth aspect, the present invention relates to a process for preparing a cosmetic or dermatological composition according to the invention, comprising at least a step of mixing the component compounds.

[0292] In the description and the following examples, unless otherwise indicated, percentages are percentages by weight, and value ranges written in the form of "...-..." include the specified minimum and maximum limits. The following examples are for reference only and do not limit the scope of the present invention.

[0293] The following examples illustrate the invention but do not limit its scope. BRIEF DESCRIPTION OF THE DRAWINGS

[0294] [ Figure 1 ] is a bar graph showing the IL-8 (pg / ml) concentration after different treatments: 1 - composition according to Example 1 (in liquid solution form); 2 - composition according to Example 1 (in liquid solution form) + Staphylococcus aureus; 3 - composition according to the cream formulation of Example 1; 4 - composition according to the cream formulation of Example 1 + Staphylococcus aureus. These data are from at least three independent experiments.

[0295] [ Figure 2 ] is a bar graph showing the IP-10 (pg / ml) concentration after the following different treatments: 1 - composition according to Example 1 (in liquid solution form); 2 - composition according to Example 1 (in liquid solution form) + Staphylococcus aureus; 3 - composition according to the cream formulation of Example 1; 4 - composition according to the cream formulation of Example 1 + Staphylococcus aureus. These data are from at least three independent experiments.

[0296] [ Figure 3 ] is a bar graph showing the IL-1β (pg / ml) concentration after the following different treatments: 1 - the composition according to Example 1 (in liquid solution form); 2 - the composition according to Example 1 (in liquid solution form) + Staphylococcus aureus; 3 - the composition according to the cream formulation of Example 1; 4 - the composition according to the cream formulation of Example 1 + Staphylococcus aureus. These data are from at least three independent experiments.

[0297] [ Figure 4 ] is a bar graph showing the IL-6 (pg / ml) concentration after different treatments: 1 - composition according to Example 1 (in liquid solution form); 2 - composition according to Example 1 (in liquid solution form) + Staphylococcus aureus; 3 - composition according to the cream formulation of Example 1; 4 - composition according to the cream formulation of Example 1 + Staphylococcus aureus. These data are from at least three independent experiments. Example

[0298] Example 1: Composition Example:

[0299] For 100 mL of the composition, the composition comprises:

[0300] - 20mg silver in total, up to 20% ionic silver and 80% colloidal silver, with an average particle size of 0.8nm.

[0301] -0.9% Sambucus nigra extract.

[0302] -5% Hypericum perforatum dry extract.

[0303] -1.5% South African geranium dry extract.

[0304] -3% Echinacea dry extract.

[0305] -4% purified propolis extract.

[0306] Example 2: Anti-inflammatory activity of the composition in Example 1.

[0307] Materials and methods

[0308] Human HT-29 epithelial cell line monolayers were grown in DMEM (Dulbecco's Modified Eagle Medium, Gibco, UK) supplemented with 10% fetal bovine serum at 37° C. and 5% CO 2. At approximately 90% confluence of the monolayer, the cells were incubated with 0.25% trypsin solution and 10 mM EDTA at 37° C. for 10 minutes.

[0309] To determine the anti-inflammatory effect, 2 × 10 5 Eukaryotic cells were cultured at a concentration of 10 cells / ml. The culture medium was changed every 2 days for a total of 14 days to promote not only the formation of a monolayer (3-4 days) but also the maturation of cell receptors. The resulting monolayer was washed twice with phosphate-buffered saline (PBS).

[0310] DMEM (1 ml) containing different formulations was added to each well and incubated at 37°C for 20 hours. The following formulations were used:

[0311] -DMEM control;

[0312] -Contains 1x10 5 CFU / ml Staphylococcus aureus in DMEM;

[0313] - DMEM containing 10% of the composition of Example 1 (in liquid solution form);

[0314] - containing 10% of the composition of Example 1 (in liquid solution form) and 1x10 5 CFU / ml Staphylococcus aureus in DMEM;

[0315] - DMEM containing 10% of the composition of the cream preparation of Example 1;

[0316] - Composition containing 10% of the cream formulation of Example 1 and 1x10 5 CFU / ml of Staphylococcus aureus in DMEM.

[0317] After incubation, cell-free supernatants were used to determine cytokine expression. IL-8, IP-10, IL-1β, and IL-6 were detected by ELISA (enzyme-linked immunosorbent assay) according to the manufacturer's instructions (Diaclone, USA).

[0318] Study Results

[0319] The results of the study showed that Staphylococcus aureus increased the concentration of pro-inflammatory cytokines IL-8 ( Figure 1 ) and IP-10( Figure 2 ) levels were increased 3-fold. IL-1β levels were reported to be approximately twice as high ( Figure 3 IL-6 had the lowest increase, about 1.5 times ( Figure 4 This finding suggests that IL-8 and IP-10 are the most sensitive markers of S. aureus-induced inflammation in these experiments.

[0320] The data showed that there was no overexpression of IL-8 after treatment with both compositions of the present invention (cream and liquid solution forms) ( Figure 1 No overexpression was detected after application of the product to a Staphylococcus aureus-induced inflammatory cell line. Similar levels were measured.

[0321] The next marker tested was IP-10. The data showed that IP-10 overexpression inhibition showed a better protective effect when the composition of Example 1 was applied without a cream (or in a liquid solution) compared to a cream ( Figure 2 ).

[0322] The same results were observed for the other tested marker, IL-1β, whose concentration decreased by 60-fold ( Figure 3 ). The composition in the form of a cream according to Example 1 reduced the induction of IL-1β by about 1.5-fold.

[0323] For IL-6, the greatest reduction was observed after application in the form of a cream according to Example 1: approximately 9-fold ( Figure 4 ). It was calculated that the reduction in IL-6 after administration of the composition of Example 1 was reduced by 6 times.

[0324] discuss

[0325] The results of the study showed that in both cases, both formulations (the composition of Example 1 in liquid solution form and the composition of Example 1 in cream form) reduced the concentrations of four pro-inflammatory cytokines:

[0326] - Control sample (DMEM); and

[0327] -Cell lines under S. aureus-induced inflammatory conditions.

[0328] Based on the reported data, we can conclude that the composition of Example 1 in liquid solution has a greater ability to reduce IL-8, IP-10, and IL-1β concentrations than the effect of the composition in cream form of Example 1. However, the composition of Example 1 in cream form proved to have a greater effect on IL-6 than the composition of Example 1 in non-cream form (liquid solution form).

[0329] References

[0330] -Agarwal,H.,&Shanmugam,V.(2020).A review on anti-inflammatory activity of green synthesized zinc oxide nanoparticles:Mechanism-basedapproach.Bioorganic chemistry,94,103423.

[0331] -Al-Daghri,NM,Yakout,S.,Al-Shehri,E.,Al-Fawaz,H.,Aljohani,N.,&Al-Saleh,Y.(2014).Inflammatory and bone turnover markers in relation to PTH andvitamin D status among Saudi postmenopausal women with and withoutosteoporosis.

[0332] Internationaljournal of clinical and experimental medicine,7(9),2812.

[0333] -Dinarello,CA.Interleukin-1.Cytokine GrowthFactorRev 1997.8:253-265.

[0334] -Greten,F.R.,&Grivennikov,S.I.(2019).Inflammation and cancer:triggers,

[0335] mechanisms,and consequences.Immunity,51(1),27-41.

[0336] -Gunalan,G.,Vijayalakshmi,K.,Saraswathy,A.,Hopper,W.,&Tamilvannan,T.

[0337] (2014).Anti-inflammatory activities ofphytochemicals from Bauhiniavariegata

[0338] Linn.leaf:An in silico approach.J.chem.pharm,6(9),334-48.

[0339] -Kolb,M.,Margetts,P.J.,Anthony,D.C.,Pitossi,F.,&Gauldie,J.(2001).Transient expression of IL-1βinduces acute lung injury and chronic repairleading to pulmonary fibrosis.TheJournal ofclinical investigation,107(12),1529-1536.

[0340] -Liu,Q.,Mazhar,M.,&Miller,L.S.(2018).Immune and inflammatory

[0341] responses to Staphylococcus aureus skin infections.Current

[0342] dermatology reports,7(4),338-349.

[0343] -Medzhitov,R.(2008).Origin and physiological roles ofinflammation.Nature,

[0344] 454(7203),428-435.

[0345] -Mueller,M.,Hobiger,S.,&Jungbauer,A.(2010).Anti-inflammatory activityof

[0346] extracts from fruits,herbs and spices.Food chemistry,122(4),987-996.

[0347] -Pathak,S.,Goldofsky,E.,Vivas,E.X.,Bonagura,V.R.,&Vambutas,A.(2011).

[0348] IL-1βis overexpressed and aberrantly regulated in corticosteroidnonresponders with autoimmune inner ear disease.The Journal of Immunology,186(3),

[0349] 1870-1879.

[0350] -Peiró,C.,Lorenzo, Carraro,R.,&Sánchez-Ferrer,C.F.(2017).IL-1βinhibition in cardiovascular complications associated to diabetesmellitus.Frontiers in

[0351] pharmacology,8,363.

[0352] -Sims,J.E.,and D.E.Smith.2010.The IL-1 family:regulators ofimmunity.

[0353] Nat.Rev.Immunol.10:89-102.

[0354] -Singh,J.K., B.M.,Howell,S.J.,Farnie,G.,&Clarke,R.B.(2013).

[0355] Recent advances reveal IL-8 signaling as a potential key to targetingbreast cancer stem cells.Breast CancerResearch,15(4),1-9.

[0356] -Tatiya-Aphiradee,N.,Chatuphonprasert,W.,&Jarukamjorn,K.(2019).

[0357] Anti-inflammatory effect of Garcinia mangostana Linn.pericarp extractin methicillin-resistant Staphylococcus aureus-induced superficial skininfection in mice.Biomedicine&Pharmacotherapy,111,705-713.

Claims

1. A composition for preventing and / or treating inflammation, comprising: -Silver in colloidal form; - Sambucus nigra extract; - Hypericum perforatum extract; - South African geranium extract.

2. Composition for use according to the preceding claims, characterized in that The particle size of the colloidal silver is 0.1 nm to 30 nm.

3. A composition for use according to any one of the preceding claims, comprising: - 20 mg to 250 mg of silver in colloidal form per liter of composition; - 0.3% to 5% by weight of an elderberry extract component; - 0.5% to 11% by weight of a Hypericum perforatum extract component; - 1% to 6% by weight of a pelargonium officinale extract component.

4. The composition for use according to any one of claims 1 and 2, further comprising: -Silver in ionic form.

5. A composition for use as a medicament according to any one of the preceding claims, comprising: - The total silver content per liter of the composition is 20 mg to 250 mg, distributed in; i. 70% to 99.99% by weight of silver in colloidal form; ii. 0.01% to 30% by weight of silver, in ionic form; - 0.3% to 5% by weight of an elderberry extract component; - 0.5% to 11% by weight of a Hypericum perforatum extract component; - 1% to 6% by weight of a pelargonium officinale extract component.

6. A composition for use according to any one of the preceding claims, further comprising: Echinacea extract, and / or - Propolis and / or - Artemisia extract and / or - garlic extract and / or -Primula calyx extract.

7. A composition for use according to any one of the preceding claims, comprising: - 0.01% to 8% by weight of Echinacea extract components, and / or - 0.01% to 7% by weight of a propolis component, and / or - 0.5% to 3% by weight of an Artemisia extract component, and / or - 0.01% to 10% by weight of garlic extract components, and / or - 1% to 9% by weight of a Primula calyx extract component.

8. A composition for use according to any one of the preceding claims, as a medicament for the prevention and / or treatment of Staphylococcus aureus induced inflammation.

9. Composition for use according to any one of the preceding claims, characterized in that It is in a form suitable for application to the skin as an ointment, cream, liquid solution, patch or gel, preferably a cream or liquid solution.

10. A non-therapeutic cosmetic use of a composition for reducing visual symptoms of inflammation on the skin of a subject, the composition comprising: -Silver in colloidal form; - Sambucus nigra extract; - Hypericum perforatum extract; - South African geranium extract.

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