阅读说明：本技术 依克多因和灵芝提取物对皮肤炎症的协同作用 (Synergistic effect of ectoin and ganoderma extract on skin inflammation ) 是由 安德鲁·菲利普·萨拉扎 乔尔格·冯·哈根 亚历山德拉里·兰 鲁楠 于 2019-09-27 设计创作，主要内容包括：本发明涉及由依克多因和从灵芝(Ganode rma)获得的提取物组成的活性混合物,以及包含所述组合物或组分的化妆品制剂、皮肤病学制剂、药物组合物或医疗设备。本发明还涉及：依克多因与从灵芝(Ganoderma)获得的提取物的组合的用途,其表现出所述提取物的抗炎活性的效力的增强,以及衍生的非治疗方法。(The present invention relates to an active mixture consisting of ectoin and an extract obtained from ganoderma lucidum (ganoderma), and to a cosmetic, dermatological, pharmaceutical or medical device comprising said composition or component. The invention also relates to: use of ectoin in combination with an extract obtained from Ganoderma lucidum (Ganoderma) showing an enhancement of the efficacy of the anti-inflammatory activity of said extract, and derived non-therapeutic methods.)

1. An active mixture consisting of ectoin and an extract obtained from Ganoderma lucidum (Ganoderma).

2. The mixture according to claim 1, wherein said extract is an aqueous extract of ganoderma lucidum.

3. Mixture according to claim 1 or 2, wherein ectoin and extract are present in a ratio of 5: 1 to 1: 5 is present.

4. Use of the active mixture according to one or more of claims 1 to 3 for the preparation of a cosmetic, dermatological or pharmaceutical composition or a medical device.

5. Active mixture according to one or more of claims 1 to 3 for use in reducing inflammation and irritation by topical application to human skin.

6. Cosmetic, dermatological or pharmaceutical composition or medical device comprising ectoin and an extract obtained from Ganoderma lucidum (Ganoderma).

7. The composition or device according to claim 6, wherein said extract is an aqueous extract of Ganoderma lucidum.

8. The formulation or device according to claim 6 or 7, wherein ectoin and extract are present in a ratio of 5: 1 to 1: 5 is present.

9. The formulation or device according to one or more of claims 6 to 8, wherein ectoin is present in an amount of 0.01 to 10% by weight of the formulation.

10. The formulation or device according to one or more of claims 6 to 9, wherein the extract is present in an amount of 0.01 to 10% by weight of the formulation.

11. A dermatological or pharmaceutical composition or a medical device according to claim 6, for use in reducing inflammation by topical application to human skin.

12. Non-therapeutic use of ectoin as an activity enhancer for extracts obtained from Ganoderma lucidum (Ganoderma lucidum).

13. Use of ectoin in combination with an extract obtained from Ganoderma lucidum (Ganoderma) showing an increase in the efficacy of the anti-inflammatory activity of said extract.

14. A non-therapeutic method for reducing or preventing inflammation and irritation by topically applying a mixture according to claim 1 or a cosmetic preparation according to claim 6 to human skin.

Technical Field

The present invention relates to an active mixture consisting of ectoin and an extract obtained from Ganoderma lucidum (Ganoderma), and to a cosmetic, dermatological or medical device comprising said composition or component. The invention also relates to: use of ectoin in combination with an extract obtained from Ganoderma lucidum (Ganoderma) showing an enhancement of the efficacy of the anti-inflammatory activity of said extract, and derived non-therapeutic methods.

Background

The epidermis is the outermost layer of the skin and is composed primarily of keratinocytes (keratinocytes). These cells differentiate upward to form a basement membrane (basal layer) where they contact the dermis, forming stratified layers (e.g., spinous and granular layers) that ultimately serve as a sheet of connected keratinocytes at the outermost position, the Stratum Corneum (SC). Each stage of epidermal differentiation is characterized by the expression of a specific protein.

The stratum corneum forms a barrier to protect the underlying tissue from infection, dehydration, chemicals and mechanical stress. Desquamation, the process by which cells are shed from the surface of the stratum corneum, balances the proliferation of keratinocytes from the basal layer.

Skin inflammation occurs in response to external influences, such as environmental stress, UV exposure, disease conditions, and aging processes. In addition to the undesirable symptoms of redness, itching and swelling, tissue damage can occur during inflammation, thereby compromising the texture and elasticity of the skin.

The NF- κ B pathway is the primary signaling pathway in inflammatory processes, induced primarily by external chemical and biological influences such as chemical, bacterial or viral antigens.

External chemical influences include in particular the influence of chemicals on the skin, in particular irritants, pollutants or heavy metals. Frequently airborne non-allergenic irritants, so-called pseudoallergens, are, for example, aerosols from adhesives, detergents or sprays, fragrances, environmental pollutants such as aromatic hydrocarbons and/or Volatile Organic Compounds (VOC) or particulate matter such as tobacco smoke, municipal dust, fine dust or particles from diesel exhaust gases or industrial exhaust gases. Particulate matter is generally defined by their average size. For example, PM 2.5 refers to particulate matter having an average size of 2.5 μm.

External biological influences include, for example, the influence of foreign organisms and their metabolites. Important biological effects include bacterial and viral antigens.

Yoon et al, Experimental and therapeutic media, 5:957-963,2013, describe that NF-. kappa.B is a major regulator of the production of proinflammatory cytokines and enzymes involved in the process of inflammation. Further described is that the ethanol extract of Ganoderma lucidum inhibits inflammatory responses by inhibiting NF-. kappa.B and toll-like receptor pathways in lipopolysaccharide-stimulated BV2 microglia.

Ganoderma sinensis (Ganoderma sinense) is also known to resolve unwanted inflammation in the skin by reducing this pathway.

Ganoderma lucidum (Ganoderma) is an important woody mushroom known for its medicinal value in China since ancient times. Ganoderma lucidum is a polypore fungus of the family Ganodermataceae, which includes about 80 species, and is not rarely from tropical regions. In the Chinese pharmacopoeia 2010, Ganoderma lucidum (Ganoderma lucidum) and Ganoderma sinense (Ganoderma sinense) are listed as Ganoderma lucidum. They are recommended for use as two different "herbal" drugs because the average content of total triterpenes in ganoderma lucidum is 10 times higher than g.

Xiao-Qiang Han et al, International Journal of Biological Macromolecules,51(2012) 597-. Chemical studies showed that this fraction consists of mannose, glucose and galactose in a molar ratio of 4.7: 27.1: 1.0. the authors found that GSP-4 can significantly stimulate the production of immunomodulatory markers.

The use of ganoderma lucidum extracts as ingredients in cosmetic compositions is known, for example from US2005180988, which smoothens human skin, reduces wrinkles and inflammation, or from WO2010012686, for anti-aging.

Ganoderma sinensis extract is known as an ingredient in cosmetic compositions, e.g. as found in CN103239383 for whitening and moisturizing, or as found in CN 107550786 for moisturizing.

The use of ectoin for various cosmetic and pharmaceutical purposes is known.

For example, WO 94/15923 describes that (S) -1,4,5, 6-tetrahydro-2-methyl-4-pyrimidinecarboxylic acid or (S, S) -1,4,5, 6-tetrahydro-5-hydroxy-2-methyl-4-pyrimidinecarboxylic acid can be used for the preparation of cosmetic compositions or medicaments, for example for the treatment of skin diseases.

Furthermore, DE4342560 describes the use of ectoin and ectoin derivatives as moisturizers in cosmetics. These products are suitable, for example, for the care of aged, dry or irritated skin.

Furthermore, DE19933466 describes ectoine and derivatives, such as hydroxyectoine, which can be used as radical scavengers in cosmetic and dermatological compositions. The composition can be used for treating and/or preventing skin aging caused by oxidative stress and inflammatory reactions associated with free radicals or pro-oxidative processes (ROS).

Further uses of ectoin and ectoin derivatives in cosmetic formulations are described, for example, in WO 00/07558, WO 00/07559, WO 00/07560 and US 7981899, for example, the care and prevention of dry and/or flaky skin, the protection of human skin from dryness and/or high salt concentrations, the protection of cells, proteins and/or biofilms of human skin, the protection of microbiota of human skin, the stabilization of skin barriers and the protection and stabilization of nucleic acids of human skin cells.

JP2002302444 discloses a formulation comprising ectoin for restoring the expression of silk fibroin gene caused by dry skin.

As reported by Buomino et al cell Stress & Chaperones (2005),10(3),197-203, ectoin upregulated heat shock proteins hsp70 and hsp70B' in mammalian cells, modulating pro-inflammatory responses. It further describes that ectoin has no effect on the proinflammatory cytokines Interleukin (IL) -1 α, IL-6, IL-8, and tumor necrosis factor α and NF- κ B and I κ B-pathways.

HSP70 is a known modulator of apoptosis and inflammation, which phosphorylates IKK kinase (IKK) by activation of NK- κ B, by activation via Protein Kinase A (PKA). This kinase activation leads to the activation and translocation of NF-. kappa.B to the nucleus (E.Zorzi et al, cancer 2011,3, 3921-. Ectoin has been shown to modulate mitochondrially-related signaling. In addition to radiation and temperature, two receptor classes, Fas and TRAIL, are triggers of mitochondrial activation that transduce signals into cells by activating intracellular DAXX or FADD domains. This activation often results in the accumulation of Reactive Oxygen Species (ROS).

There remains a need to find a good solution to reduce or prevent inflammation and irritation, preferably receptor mediated inflammation via TNFR, which preferably results from chemical or biological effects, particularly preferred receptor mediated inflammation via TNFR, which results from: aromatic hydrocarbons and/or Volatile Organic Compounds (VOCs) or particulate matter such as tobacco smoke, municipal dust, fine dust or particles from diesel exhaust or industrial exhaust, bacterial or viral antigens.

It is therefore an object of the present application to provide such a solution.

Summary of The Invention

The present inventors have now found that the above objects can be achieved by the process described herein or by the specific mixtures of the present application.

Ectoin was found to synergistically enhance the anti-inflammatory properties of extracts of Ganoderma lucidum (Ganoderma lucidum), preferably Ganoderma lucidum (Ganoderma lucidum).

It was surprisingly found that ectoin in combination with the extract modulates TNFR-related anti-apoptotic responses via the TRADD domain.

The present invention therefore relates to an active mixture consisting of ectoin and an extract obtained from Ganoderma lucidum (Ganoderma), preferably Ganoderma lucidum (Ganoderma lucidum).

The invention also relates to the use of the active mixture for preparing a cosmetic, dermatological or pharmaceutical composition or a medical device.

The invention also relates to a cosmetic, dermatological or pharmaceutical composition or a medical device comprising ectoin and an extract obtained from Ganoderma lucidum (Ganoderma), preferably from Ganoderma lucidum (Ganoderma lucidum).

The invention also relates to the use of ectoin in combination with an extract obtained from Ganoderma lucidum (Ganoderma), preferably from Ganoderma lucidum (Ganoderma lucidum), which exhibits an increased efficacy of the anti-inflammatory activity of said extract.

The present invention also relates to a non-therapeutic method for reducing or preventing inflammation and irritation, preferably receptor-mediated inflammation through TNFR, preferably induced by chemical, bacterial or viral antigens, by topically applying to human skin an active compound or a cosmetic composition comprising ectoin and an extract obtained from Ganoderma lucidum (Ganoderma), preferably from Ganoderma lucidum (Ganoderma lucidum).

The invention also relates to a non-therapeutic method for preventing inflammation and irritation, preferably receptor-mediated inflammation, preferably induced by chemical, bacterial or viral antigens, by topically applying to human skin an active compound or a cosmetic composition comprising ectoin and an extract obtained from Ganoderma lucidum (Ganoderma), preferably Ganoderma lucidum (Ganoderma lucidum).

The invention also relates to the non-therapeutic use of ectoin as an activity enhancer for extracts obtained from Ganoderma lucidum (Ganoderma), preferably from Ganoderma lucidum (Ganoderma lucidum).

Drawings

FIG. 1 shows the luminescence of the measured media as described in example 1.

Detailed Description

"active mixture" in the sense of the present invention means a mixture of said components which has a synergistic effect on skin cells, preferably on human skin cells.

Ectoin is a low molecular weight cyclic amino acid derivative that can be isolated or synthetically prepared from various halophilic microorganisms. Ectoin has the advantage of not reacting with cellular metabolism.

Ectoin refers to (S) -1,4,5, 6-tetrahydro-2-methyl-4-pyrimidinecarboxylic acid, CAS number 96702-03-3.

Ectoin is commercially available and each quality can be used without limitation. Ectoine is commercially available, for example from Merck KGaA, DamschtattEctoin, from bitopBioecto from Bloomage Biotechnology^TMOf Ectoin, or UnipromaEctoine。

The preparation of ectoin is described in the literature (DE 4342560). (S) -1,4,5, 6-tetrahydro-2-methyl-4-pyrimidinecarboxylic acid can also be obtained by microbial methods (Severin et al, J.Gen.Microb.138(1992)1629-1638 or EP 1409707A).

As disclosed, the active mixture consisting of ectoin and an extract from Ganoderma lucidum (Ganoderma lucidum), preferably Ganoderma lucidum (Ganoderma lucidum), is characterized in that the Ganoderma lucidum extract is an aqueous extract.

More than 150 compounds are described in the literature for ganoderma lucidum. Preferably, the Ganoderma water extract contains 87% carbohydrate, such as beta-glucan, fructose, mannitol, 10% phenol derivative, such as gallic acid, stilbene, 2% tannin and 1% alkaloids, flavonoids, and saponins as main components. Preferred aqueous extracts of Ganoderma lucidum exhibit a mixture of polar and less polar substances which absorb in the UV.

Dried fruiting bodies of Ganoderma lucidum (Ganoderma lucidum) or Ganoderma sinense (Ganoderma sinense) are commercially available. The extraction with water is based on stages common in the field of extraction and the person skilled in the art is able to adjust its parameters based on general knowledge.

The ganoderma lucidum extract can be preferably obtained by a method comprising the steps of:

-providing dried fruiting bodies of ganoderma lucidum, and

extraction with water at 100 ℃.

The extraction process may be followed by ultrafiltration, nanofiltration, reverse osmosis and/or spray drying.

Alternatively, aqueous extracts of Ganoderma (Ganoderma lucidum) or Ganoderma sinense (Ganoderma sinense) are commercially available.

Preferred ganoderma lucidum extracts are preferably those commercially available from Draco Natural Products, Inc.

The present invention further relates to an active mixture as described previously or preferably wherein ectoin and ganoderma lucidum extract are present in a ratio of 5: 1 to 1: 5, preferably in a weight ratio of 3: 1 to 1: 3 (by weight), particularly preferably 1: 1 (by weight).

The invention further relates to the use of said active mixture as described previously or preferably with the components as described previously for the preparation of a cosmetic, dermatological or pharmaceutical composition or a medical device.

The cosmetic, dermatological or pharmaceutical composition or medical device may comprise the active mixture as described previously or preferably in an amount of from 0.01 to 10% by weight, preferably from 0.1 to 5% by weight, more preferably from 0.5 to 3% by weight, based on the total weight of the composition.

The invention also relates to a cosmetic, dermatological, pharmaceutical composition or medical device comprising ectoin and an extract of Ganoderma lucidum (Ganoderma) as described previously or preferably.

In the cosmetic, dermatological or pharmaceutical composition or medical device, the total weight content of ectoin is from 0.01 to 10% by weight, preferably from 0.1 to 5% by weight, more preferably from 0.5 to 3% by weight, based on the total weight of the composition or device.

In the cosmetic, dermatological or pharmaceutical composition or medical device, the total weight content of the ganoderma lucidum extract is from 0.01 to 10% by weight, preferably from 0.1 to 5% by weight, more preferably from 0.5 to 3% by weight, based on the total weight of the composition or device.

In the cosmetic, dermatological or pharmaceutical composition or medical device, ectoin and ganoderma lucidum extract are present in a ratio of 5: 1 to 1: 5, preferably in a weight ratio of 3: 1 to 1: 3, particularly preferably in a weight ratio of 1: a ratio of 1 is present.

For the purposes of the present invention, the term "composition" is also used synonymously with the term "formulation".

The formulations herein are generally cosmetic or dermatological formulations, which may be applied topically. By "topically applicable" is meant that the formulation is applied externally and topically, i.e., the formulation must be suitable, e.g., capable of being applied to the skin. In this case, the formulation comprises a cosmetically, pharmaceutically or dermatologically suitable carrier and, depending on the desired property profile, optionally also other suitable ingredients. The topical formulations are preferably used as cosmetic compositions. Suitable carriers and adjuvants or fillers are known in the art.

The preparations according to the invention may also contain abrasives, anti-acne agents, anti-skin ageing agents, anti-cellulite agents, anti-dandruff agents, anti-inflammatory agents, irritation-preventing agents, irritation-inhibiting agents, antioxidants, astringents, perspiration-inhibiting agents, preservatives, antistatic agents, binders, buffers, carrier materials, chelating agents, cell-stimulating agents, cleaning agents, care agents, depilatory agents, surfactants, deodorants, antiperspirants, emollients, emulsifiers, enzymes, essential oils, fibers, film-forming agents, fixatives, foam-forming agents, foam stabilizers, foam-preventing substances, foam boosters, gelling agents, gel-forming agents, hair care agents, hair-setting agents, hair-straightening agents, moisturizers, moisturizing substances, bleaching agents, reinforcing agents, dye-removing agents, optical brighteners, impregnating agents, anti-soiling agents, friction-reducing agents, lubricants, opacifiers, plasticizers, coating agents, polishing agents, shine agents, polymers, proteins, re-lubricants, abrasives, silicones, skin soothing agents, skin cleansers, skin protectants, skin rejuvenating agents, skin lightening agents, skin care agents, skin softeners, hair boosters, cooling agents, skin cooling agents, warming agents, skin warming agents, stabilizers, uv absorbers, organic uv filters, inorganic uv filters, detergents, fabric conditioners, suspending agents, skin tanning agents, thickeners, vitamin oils, waxes, fats, phospholipids, saturated fatty acids, mono-or polyunsaturated fatty acids, alpha-hydroxy acids, polyhydroxy fatty acids, liquefying agents, dyes, color protection agents, pigments, preservatives, fragrances, flavoring substances, odorous substances, polyols, surfactants or electrolytes.

Particularly suitable for the combinationThe active ingredient is hydroxyectoin, trehalose, glycerol, glycosylglycerol, β -mannosylglycerol (firoin), β -mannosylglycamide (firoin a), di-phosphoinositide (DIP), cyclic 2, 3-diphosphoglyceric acid (cDPG), 1, 1-diglyceryl phosphate (DGP), di-mannosylinositol Diphosphate (DMIP), betaine, glycine betaine, proline betaine, glutamic betaine, alanine, proline, glutamine, N-acetyl lysine, glutamine 1-amide, taurine, choline O-sulfate, carnitine, arsenic betaine, crotonobetaine, dimethyl sulfoacetate, dimethyl sulfonate, high betaine, trimethylamine N-oxide, panthenol, sorbitol, meglumine, hyaluronic acid or hyaluronic acid derivatives, urea.Urea) and nicotinamide (Niacinamide), 5, 7-dihydroxy-2-methylchromone, tradenameMarketed or commercial products RenouMer，VTA，Poppy SE，Isoquercetin，Cyclopeptide 5，The Cyclopeptide 5 is alcohol-free,SereneShield，Emblica，orA liquid.

The formulation may comprise or comprise, consist essentially of or consist of the essential or optional components mentioned above and/or below. All compounds or components useful in the formulations are known and commercially available or may be synthesized by known methods.

These further active ingredients are preferably present in the topical formulations in an amount of from 0.01 to 20% by weight, particularly preferably from 0.1 to 15% by weight, very particularly preferably from 0.2 to 8% by weight, based on the total amount of the formulation.

Organic uv filters, so-called hydrophilic or lipophilic sunscreen filters, are effective in the UVA region and/or the UVB region and/or the IR and/or VIS region (absorbers). These substances can be chosen in particular from dibenzoylmethane derivatives, cinnamic acid derivatives, salicylic acid derivatives, camphor derivatives, triazine derivatives, beta-diphenylacrylate derivatives, p-aminobenzoic acid derivatives and polymeric and silicone filters. The UV filters are generally named according to INCI nomenclature as follows.

Particularly suitable for combination with the active mixtures according to the invention are ethylhexyl salicylate, phenylbenzimidazole sulfonic acid, benzophenone-3, benzophenone-4, benzophenone-5, 2- (4-diethylamino-2-hydroxybenzoyl) n-hexyl benzoate, 4-methylbenzylidene camphor, terephthaloyldicamphor sulfonic acid, disodium phenyldibenzoimidazole tetrasulfonic acid, methylenebis (benzotriazolyl) tetramethylbutylphenol, butylmethoxydibenzoylmethane, ethylhexyltriazone, diethylhexylbutamidotriazone, triazolocyclotrisiloxane, phenylenebiphenyltriazine, polysiloxane-15, 1, 1-dicarboxyl (2,2' -dimethylpropyl) -4, 4-diphenylbutadiene, 2, 4-bis [5-1 (dimethylpropyl) benzoxazol-2-yl (4-phenylbistriazine) ) Imino ] -6- (2-ethylhexyl) imino-1, 3, 5-triazine, and mixtures thereof. These organic UV filters are generally incorporated in the formulations in amounts of from 0.01% to 20% by weight, preferably from 1% to 10% by weight.

The formulations may preferably comprise adjuvants, such as cosmetic oils (e.g. caprylic/capric triglyceride, C12-15 alkylbenzoate, isopropyl myristate, arylalkyl benzoate, e.g. phenethylbenzoate (X-Tend 226) or cosmecol brand oil components such as dimyristol tartrate, tri C14-C15 alkyl citrate, C12-C13 alkyl lactate, tridecyl salicylate, C12-C13 alkyl octanoate, C12-C13 alkyl malate, C12-C13 alkyl citrate, C12-C13 alkyl tartrate, or polar-protic adjuvants (e.g. propylene glycol, glycerol, isopropanol, ethanol) or so-called solubilizers (e.g. butylphthalimide, isopropylphthalimide, dimethyl isosorbide.) very particularly preferred cosmetic oils are C12-C13 alkyl lactate (available under the trade name cosmecol ELI), and phenethyl phenylacetate (available under the trade name X-Tend 226).

The formulations as described above can be synthesized by mixing the active mixtures according to the invention or the individual components of the active mixtures with carriers suitable for such formulations and optionally with auxiliaries and/or fillers. Suitable carriers and adjuvants or fillers are described in detail in the following sections.

The components of the formulation may be incorporated in a conventional manner by means of techniques well known to those skilled in the art.

Formulations suitable for external use can be applied or sprayed onto the skin, for example as creams or milks (O/W, W/O, O/W/O, W/O/W, W/Si), as lotions or emulsions, in the form of oil-alcohol, oil-water or water-alcohol gels or solutions. They may be in the form of solid sticks or formulated as aerosols. They may be shampoos, body washes, face cleansers or essences.

Hereinafter, for example, application forms as formulations to be used may be mentioned: solutions, suspensions, emulsions, PIT's emulsions, pastes, ointments, gels, creams, lotions, powders, oils, aerosols, plasters, compresses, bandages and sprays.

Preferred adjuvants are from the group of preservatives, stabilizers, solubilizers, colorants, odor improvers, thickeners, plasticizers, humectants, surfactants, emulsifiers, preservatives, antifoams, fragrances, waxes, lanolin, propellants and other ingredients customary in cosmetics.

Ointments, pastes, creams and gels may contain conventional carriers suitable for topical application, for example animal and vegetable fats, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silica, talc and zinc oxide, or mixtures of these substances.

Powders and sprays can contain conventional carriers such as lactose, talc, silica, aluminum hydroxide, calcium silicate and polyamide powder, or mixtures of these substances. Sprays can additionally contain customary volatile liquefied propellants, for example chlorofluorohydrocarbons, propane/butane or dimethyl ether. Compressed air may also be advantageously used.

Solutions and emulsions may contain conventional carriers such as solvents, solubilizers and emulsifiers, for example water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1, 3-butylene glycol, oils, in particular cottonseed oil, peanut oil, wheat germ oil, olive oil, castor and sesame oil, XTend 226, glycerol fatty acid esters, fatty acid esters of polyethylene glycol and sorbitan, or mixtures of these substances.

Suspensions may include conventional carriers such as liquid diluents, for example water, ethanol or propylene glycol, suspending media, for example ethoxylated isostearyl alcohols, polyoxyethylene sorbitol esters and polyoxyethylene sorbitan esters, microcrystalline cellulose, aluminium metahydroxide, bentonite, agar-agar and tragacanth, or mixtures of these substances.

The facial and body oils may contain conventional carriers such as synthetic oils, for example fatty acid esters, fatty alcohols, silicone oils, natural oils, for example vegetable oils and oily plant extracts, paraffin oils, lanolin oils or mixtures of these substances.

Further typical cosmetic application forms are lipsticks, lip care sticks, powder cosmetics, emulsion cosmetics and wax cosmetics, as well as sunscreens, pre-and post-sun preparations.

Preferred formulation forms also include in particular emulsions.

Emulsions are advantageous and include, for example, the fats, oils, waxes and other fatty substances, as well as water and emulsifiers, as are commonly used in such formulations. Emulsifiers which can be used are, for example, the known W/O and O/W emulsifiers. It is advantageous to use other conventional coemulsifiers in the preferred O/W emulsions.

Preferred oils and/or lipids for use in the topical formulation include: paraffin wax, isoparaffin, dioctyl ether, PPG-15, stearyl ether, beeswax, candelilla wax, carnauba wax, ethylhexyl stearate, caprylic/capric triglyceride, cetyl lactate, stearic stearate, isononyl isononanoate, octyldodecanol, hexyldecanol, squalene, natural triglycerides such as cherry kernel oil (Prunus Cerasus), avocado oil, safflower seed oil, macadamia nut oil, cocoa butter (Theobroma Cacao), shea butter and mixtures thereof.

Preferred absorbing and/or thickening agents for use in the formulations include modified corn starch, silica, talc, zinc stearate, magnesium sulfate, zinc oxide, calcium and aluminum borosilicates, starch and derivatives, polyurethanes, and mixtures thereof.

As previously mentioned, ectoin is able to increase the efficacy of the anti-inflammatory activity of the ganoderma lucidum extract as previously described or as previously preferably described.

The invention therefore also relates to the non-therapeutic use of ectoin as an activity enhancer for extracts obtained from Ganoderma lucidum (Ganoderma) as described previously or preferably.

Thus, the present invention also relates to the use of ectoin in combination with an extract obtained from Ganoderma lucidum (Ganoderma) as described previously or preferably.

The invention therefore also relates to the use of ectoin in combination with an extract obtained from Ganoderma lucidum (Ganoderma) as described previously or preferably, showing an increased efficacy of the anti-inflammatory activity of said extract.

Thus, the present invention also relates to a non-therapeutic method for reducing or preventing inflammation and irritation by topically applying to the human skin an active mixture as described previously or preferably.

Thus, the present invention also relates to a non-therapeutic method for preventing inflammation and irritation mediated by receptors of the TNFR by topically applying to human skin an active mixture as described previously or preferably.

Thus, the present invention further relates to a non-therapeutic method of reducing or preventing inflammation and irritation by topically applying to the human skin a cosmetic composition comprising an active mixture as described or preferred above or a cosmetic composition comprising components of an active mixture as described or preferred above.

Thus, the present invention further relates to a non-therapeutic method of reducing or preventing inflammation and irritation mediated via receptors of TNFR by topically applying to human skin a cosmetic composition comprising an active mixture as described or preferred or a cosmetic composition comprising components of an active mixture as described or preferred.

The invention therefore also relates to an active mixture as described previously or preferably for use in reducing inflammation and irritation by topical application to human skin.

Thus, the present invention also relates to an active mixture as described previously or preferably for use in reducing inflammation and irritation mediated by receptors via TNFR by topical application to human skin.

The invention therefore also relates to a dermatological or pharmaceutical composition or a medical device comprising the components of the active mixture as described previously or preferably for reducing inflammation and irritation by topical application to human skin.

The invention therefore also relates to a dermatological or pharmaceutical composition or a medical device comprising the components of the active mixture as described previously or preferably for reducing inflammation and irritation mediated via receptors of TNFR by topical application to human skin.

Preferably, the active mixture or a composition comprising the active mixture or a component comprising the mixture as described hereinbefore is capable of reducing inflammation mediated via receptors of TNFR. Particularly preferably, the active mixture as described hereinbefore or a composition comprising the active mixture or a component comprising the mixture is capable of reducing inflammation mediated via receptors of TNFRs, as induced by: aromatic hydrocarbons and/or Volatile Organic Compounds (VOCs) or particulate matter, such as tobacco smoke, municipal dust, fine dust or particles in diesel exhaust or industrial gases, bacterial or viral antigens.

This application is carried out using standard techniques, for example by applying shampoos, shower gels, creams, face washes, pastes, gels, lotions, essences to the skin to be treated, or dissolving a predetermined amount of a preparation comprising an active mixture as described previously or an active mixture as described previously in water and subsequently using the foam mixed or formed from said water for cleansing or skin treatment.

It should be noted that variations of the embodiments described in the present invention are included in the scope of the present invention. Any feature disclosed in this specification may be replaced by an alternative feature serving the same purpose, or an equivalent or similar purpose, unless expressly excluded. Thus, unless expressly stated otherwise, any feature disclosed in this specification is to be considered as an example of a generic series of equivalent or similar features.

All of the features of the present invention may be combined with each other in any manner, unless the specific features and/or steps are mutually exclusive. This is particularly true for the preferred features of the present invention. Also, features that are not necessarily combined may be used separately (rather than in combination).

The technical teachings disclosed herein may be abstracted away and combined with other examples.

The complete disclosures of all applications and publications mentioned above and below are incorporated by reference into this application.

The following examples are intended to illustrate the invention. However, they should in no way be considered limiting.

Examples

Materials and methods:

ganoderma lucidum extracts were obtained from Draco Natural Products, Inc. The extract is hereinafter designated GS.

Ectoin obtained from Merck, Darmstadt (Art.130200)Ectoin. The product is hereinafter referred to as Ectoin.

The active mixture used in example 1 was a mixture of GS and econin in a weight ratio of 1: 1. The mixture is hereinafter referred to as GS + echoin.

NF-. kappa.B activation assay: pGL4.32[ luc 2P/NF-. kappa.B-RE/Hygro ] luciferase reporter gene was stably integrated in the GloResponse NF-. kappa.B-RE-luc 2P HEK293 cell line (Promega). pGL4.32[ luc 2P/NF-. kappa.B-RE/Hygro ] vector contains 5 copies of NF-. kappa.B responsive element (NF-. kappa.B-RE, which drives transcription of luciferase reporter gene luc2P (Photinus pyralis)). L uc2P is a synthetically derived luciferase sequence with humanized codon optimization designed for high expression and reduced aberrant transcription. The luc2P gene contains hPEST, a protein destabilizing sequence. The protein encoded by luc2P responded faster than the protein encoded by the luc2 gene upon induction. Luciferase activity was measured on a Tecan Spark 20M luminometer (Tecan, Switzerland) using One-Glo luciferase assay System reagent (Promega) according to the manufacturer's instructions.

Example 1:

in the following experiments, the anti-inflammatory potential of the fractions was tested using the NF-. kappa.B-RE-luc 2P HEK293 cell line, a cloned derivative of human embryonic kidney 293(HEK293) cells. These cells contain a luciferase gene (luc2P) under the control of a minimal TATA promoter with multiple nuclear factor- κ B response elements (NF- κ B-RE). NF-. kappa.B-RE is a DNA binding sequence of NF-. kappa.B transcription factor, which is responsible for regulating inflammation, immune response, cell growth and apoptosis. Activation of RE is indicated by an increase in luminescence in the reporter cell assay.

NF-. kappa.B-RE-luc 2P HEK293 cells at 37 ℃ and 5% CO₂In DMEM (Thermo Fisher, Germany) supplemented with 10% FCS (Biochrome, merck, Germany). The inoculation density is 1X 10⁴/cm². The cells were cultured for 24 hours after the addition of the treatment and stimulated with TNF α for 5 hours. After stimulation, luciferase reagents were added. Statistics were performed using one-sided ANOVA.

In this experiment, activation of NF-. kappa.B was rigorously induced by stimulation with TNF α alone, which binds to TNFR and internally activates the TRADD domain, resulting in activation of the MAP kinase signaling cascade. This pathway is not directly regulated by HSP70, so the effect in this example is not related to HSP70 activation reported by Buommino et al.

As a result:

as shown in figure 1, treatment of reporter cells with GS showed a 47% reduction compared to untreated, and a 46% reduction in dexamethasone treatment compared to dexamethasone. Ectoin showed no reduction (109.8%), while the combination of GS and ectoin showed a synergistic statistically significant 66.9% reduction in NF- κ B activation.

Ectoin showed no reduction in NF- κ B as monotherapy, but the combination showed a higher reduction, 20% more than monotherapy, these data demonstrate a synergistic effect.

The combinations tested showed a synergistic effect, as the use of the ectoin treatment (RFU 1098,26) as a single treatment did not show a reduction in NF- κ B compared to the control (RFU 1086, 49). Treatment with GS after TNF α -induced inflammation can reduce NF- κ B activation from 556,31RFU to 530, 02. The combination was able to synergistically reduce NF- κ B activity by 14% (RFU 331,02) compared to the control.

Formulation examples

Example 1: O/W daytime care formula

The procedure is as follows:

solaglum AX was dispersed in water and stirred until homogeneous. Adding ectoin and glycerin, and stirring to uniform.

Phase A and phase B were heated to 80 ℃ separately. Stir phase B into phase a. And (6) homogenizing. Cooling while stirring. Dissolving the C phase antiseptic in water and adding Ganoderma extract. Add phase C to the emulsion at 40 ℃. Finally, phase D was adjusted to pH 6.00.

Suppliers of goods

(1)Merck KGaA,Darmstadt,Germany/EMD Performance Materials,(2)Seppic,(3)Gattefossé(Deutschland)GmbH,(4)BASF AG,(5)Greentech SA,(6)Croda,(7)Draco Natural Products,Inc

Example 2: W/O night care formula

The procedure is as follows:

phase A and phase B were heated to 75 ℃. Stir phase a into phase B. And (6) homogenizing. Cooling while stirring. The ingredients of phase C were added stepwise below 40 ℃.

Suppliers of goods

(1)Merck KGaA,Darmstadt,Germany/EMD Performance Materials,(2)Dr.Straetmans,(3)BASF AG,(4)Gustav Heess GmbH,(5)Evonik Nutrition&Care GmbH,(6)IOI Oleo GmbH,(7)ISP Global Technologies,(8)Draco Natural Products,Inc

Example 3: W/O BB formula with sun protection

The procedure is as follows:

phase A1 was heated to 70-80 ℃. The a2 phase was added to the a1 phase while stirring. Heating the A phase and the B phase to 70-80 ℃. Phase B was added slowly to phase a with vigorous mixing. Phase C was added at 40 ℃. And cooling to room temperature.

Suppliers of goods

(1)Merck KGaA,Darmstadt,Germany/EMD Performance Materials,(2)Evonik Nutrition&Care GmbH,(3)H.Erhard Wagner GmbH,(4)BASF AG,(5)Biesterfeld,(6)Gustav Heess GmbH,(7)S.Goldmann GmbH&Co.KG