JP7391396B2 - Noriflorum extract and its use - Google Patents

Description

The present invention relates to a novel use of extracts of the genus Aspergillus, and in particular to the use of said extracts of the genus Aspergillus in the manufacture of compositions for anti-inflammatory and skin whitening.

The genus Sarcodia is mainly distributed in the Indian Ocean and the Western Pacific region. The genus Acerium is a heterotrophic marine macroalgae and has a high content of micronutrients. For this reason, in Japan it is also called a longevity food, and in Europe and the United States, the genus Aspergillus is considered to be a representative sea vegetable. Currently, most of the uses of the genus Aspergillus are as edible as is or as food additives. Although the genus Aspergillus has a long history of being used as food, there is very little research on its effects.

The skin care products market is rapidly growing with the recent rapid development of aesthetic medicine. Factors that induce consumers to purchase skin care products include novelty, sustainability, and effectiveness. Medicinal cosmetics serve as an intermediary between doctors and cosmetic scientists with a background in the chemical industry. Cosmeceuticals have been verified by in vitro or in vivo experiments to provide further specific application value or to have better effects than conventional cosmetics. In recent years, the word "cosmeceuticals" has appeared in many advertisements and promotions, and has come to be interposed between general cosmetics and pharmaceuticals. Compared with general cosmetics, the bioactive ingredients contained in medicinal cosmetics have more distinct mechanisms of action and activities, and provide benefits similar to those of drugs.

Therefore, the industrial applicability of skin care products is high, and in particular, modern people have a high need for skin care products. In contrast, at present there is no application of active extracts of the genus Trifolium to the skin. Therefore, there is a lot of room for research and development in the genus Aspergillus.

In the present invention, an alcoholic extract is obtained by drying Noriflora and then extracting with alcohol. Next, the alcoholic extract is immersed in water and suspended to obtain an aqueous extract. Then, the aqueous extract is partitioned and extracted using ethyl acetate to form an ethyl acetate layer and an aqueous layer, and then the aqueous layer is collected. Further, the obtained aqueous layer is partitioned and extracted with 1-butanol to form a 1-butanol layer and an aqueous layer. Subsequently, the aqueous layer is collected to obtain a Noriflorum extract EH.

In a skin whitening experiment, the Acerium extract EH was able to reduce the amount of melanin expressed in cells and zebrafish bodies. These results showed that the Acerium extract EH can achieve a whitening effect by suppressing the expression of melanin.

In anti-inflammatory experiments, the Noriflora extract EH suppressed the expression of inflammatory factors cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). It was possible. These results showed that the Acerium extract EH can achieve anti-inflammation by suppressing the expression of inflammatory factors.

In an atopic dermatitis experiment, the Acerium extract EH was able to improve symptoms of atopic dermatitis (eg, symptoms such as erythema, edema, epidermal peeling, and dryness) in mice. In addition, the Noriflora extract EH was able to reduce the IgE expression level that increased due to atopic dermatitis. In addition, atopic dermatitis causes the spleen and lymph nodes to swell, and by administering the Noriflora extract EH, it was possible to improve the swelling of the spleen and lymph nodes. These results showed that the Noriflorum extract EH can treat atopic dermatitis.

The terms "a" or "a" herein are used to describe members and components of the present invention. This terminology is used only for convenience of description and to indicate the basic idea of the invention. Such descriptions should be construed as including one or at least one, and unless expressly specified otherwise, references to the singular include the plural. Also, when used in conjunction with the term "comprising" in the claims, the term "one" can mean one or more than one.

In this text, the term "or" as used in the claims means "and/or". However, this excludes cases where it is clearly indicated that the option is limited to another option, or where the option is mutually exclusive with other options.

The present invention provides a method for producing a Noriflorum extract. The method includes the following steps. That is, (a) extracting the genus Aspergillus with an alcohol-based solvent to obtain an alcoholic extract of the genus Aspergillus. The alcoholic solvent is methanol or ethanol. (b) After forming an organic solvent layer and an aqueous layer by distributing and extracting the alcoholic extract of the genus Acerium using an organic solution or supercritical extraction, the aqueous layer is collected. The organic solution is an organic solvent or a mixture of water and an organic solvent. The organic solvent is ethyl acetate, propyl acetate, butyl acetate, hexane, heptane, octane, nonane, methyl ether, ethyl ether, dichloromethane, chloroform or carbon tetrachloride. (c) The aqueous layer obtained in step (b) is partitioned and extracted with 1-butanol to form a 1-butanol layer and an aqueous layer. Subsequently, the aqueous layer is collected to obtain the Noriflora extract.

In a specific embodiment, the genus Sarcodia is Sarcodia ceylanica.

In another specific embodiment, the alcoholic solvent is ethanol. In a preferred embodiment, the alcoholic extract of the genus Aspergillus is an ethanolic extract of the genus Aspergillus.

In a specific embodiment, the organic solvent is ethyl acetate. In the present invention, since the extract of the genus Attica is obtained by collecting it from the aqueous layer, the extract of the genus Attica is an aqueous extract of the genus Attica.

In a specific embodiment, the method includes step (a1) before step (a). In the step (a1), the Acerium spp. is dried. In a preferred embodiment, the Acerium spp. is dried at a temperature of 20-70°C. In a more preferred embodiment, the Acerium spp. is dried at a temperature of 40-60°C. In another specific embodiment, the Trifolium spp. is dried at 50°C.

In a specific embodiment, the drying time of the Trifolium spp. is 12 to 48 hours. In a preferred embodiment, the drying time of the Trifolium spp. is 16 to 32 hours. In a preferred embodiment, the drying time of the Trifolium spp. is 20 to 24 hours.

In the present invention, after drying the Acerium genus, it is filtered through a filter net having a predetermined mesh pore size, and after the filtration, it is extracted with ethanol. In a specific embodiment, the method includes step (a2) before step (a). In the step (a2), the genus Acerium is filtered through a filter net having a pore size of 30 to 70 mesh. In a preferred embodiment, the method includes step (a2) before step (a). In the step (a2), the genus Acerium is filtered through a filter net having a pore size of 40 to 60 mesh. In a more preferred specific embodiment, the method comprises step (a2) before said step (a). In step (a2), the genus Acerium is filtered through a filter net with a pore size of 50 mesh.

In another specific embodiment, the Acerium spp. is extracted with an alcoholic solvent at room temperature. In a preferred embodiment, in step (a), the Acerium spp. is extracted three times by immersing it in an alcoholic solvent. Then, the immersion liquids for three times are combined, filtered, and concentrated under reduced pressure to obtain the alcoholic extract of the genus Aspergillus.

In a specific embodiment, in step (b), an organic solvent layer and an aqueous layer are formed by partitioning and extracting the alcoholic extract of the genus Acerinica with the organic solution, and then the aqueous layer is collected. In a preferred embodiment, step (b) involves distributing and extracting the alcoholic extract of the genus Acerinica with the organic solution. Moreover, by repeating the partition extraction operation three times to form an organic solvent layer and an aqueous layer, the aqueous layer is collected.

In another specific embodiment, said step (b) further comprises a step (b1) before said extraction with said organic solution. In the step (b1), the alcoholic extract of the genus Aspergillus is immersed in water to obtain an aqueous solution of the genus Aspergillus. In a preferred embodiment, in the step (b1), the alcoholic extract of the genus Aspergillus is immersed in water so that the alcoholic extract of the genus Aspergillus is suspended in the water. After performing step (b1), in the original step (b), the Acerium aqueous solution obtained in step (b1) is distributed and extracted with the organic solvent without using the mixture of water and organic solvent. . Thereby, after forming an organic solvent layer and an aqueous layer, the aqueous layer is collected.

In a specific embodiment, in step (c), the aqueous layer obtained in step (b) is partitioned and extracted with said 1-butanol. In addition, the 1-butanol layer and the aqueous layer are formed by repeating the distribution extraction operation three times, and then the aqueous layer is collected to obtain the Noriflorum extract.

After performing step (b1), in the original step (b), the aqueous solution obtained in step (b1) is partition-extracted by the supercritical extraction. In a specific example, in step (b), an organic solvent layer and an aqueous layer are formed by distributing and extracting the Acerium aqueous solution obtained in step (b1) using the supercritical extraction, and then the aqueous layer is collected. do. In another specific embodiment, the supercritical extraction is supercritical _CO2 extraction. In the present invention, in the process of separating nutritional components of natural products by supercritical CO ₂ extraction, nutritional components are extracted from natural products under high pressure and low temperature conditions, mainly using carbon dioxide fluid in a supercritical state. In a specific embodiment, the supercritical CO ₂ extraction conditions include a flow rate ratio of CO ₂ :99% ethanol solution=10 mL/min:1 mL/min, a critical pressure range of 150-400 bar, and a critical temperature. The range is 20 to 60°C. In a preferred embodiment, the supercritical CO ₂ extraction conditions include a flow rate ratio of CO ₂ :95% ethanol solution=10 mL/min:1 mL/min, a critical pressure of 250 bar, and a critical temperature of 40°C. shall be. Supercritical CO ₂ extraction similarly separates the raw material remaining in the supercritical CO ₂ extraction reaction tank (aqueous layer) and the substance to be extracted (organic solvent layer). Therefore, the aqueous layer in the supercritical CO ₂ extraction reaction tank is extracted with 1-butanol to obtain the Acerium extract.

In the present invention, in step (c), after collecting the aqueous layer from the 1-butanol layer and the aqueous layer extracted and separated with 1-butanol, the aqueous layer is first filtered through a C18 glass column to remove excess salts. is removed and then dried to obtain the Acerium extract. In a specific embodiment, the method includes step (d) after step (c). In the step (d), the aqueous layer obtained in the step (c) is filtered, and after the filtration, the extract is dried. In a preferred embodiment, the method comprises step (d) after step (c). In step (d), the aqueous layer obtained in step (c) is filtered through a C18 glass column, and after filtration, the extract is obtained by drying.

In another specific embodiment, the components of the Trifolium extract do not include polysaccharides.

The present invention further provides the use of a Noriflorum extract in the manufacture of a composition for skin whitening. The method for producing the Noriflorum extract includes the following steps. That is, (a) extracting the genus Aspergillus with an alcohol-based solvent to obtain an alcoholic extract of the genus Aspergillus. The alcoholic solvent is methanol or ethanol.

In a specific embodiment, the Acerium in step (a) is washed, dried and/or pulverized.

In another specific embodiment, the method for producing a Noriflora extract further comprises step (b) after step (a). In the step (b), an organic solvent layer and an aqueous layer are formed by distributing and extracting the alcoholic extract of the genus Salmonella using an organic solution or supercritical extraction. Subsequently, the aqueous layer is collected to obtain a Noriflora aqueous extract. The organic solution is an organic solvent or a mixture of water and an organic solvent. The organic solvent is ethyl acetate, propyl acetate, butyl acetate, hexane, heptane, octane, nonane, methyl ether, ethyl ether, dichloromethane, chloroform or carbon tetrachloride.

In a specific embodiment, the method for producing a Noriflora extract further includes step (b1) before the extraction with the organic solution. In the step (b1), the alcoholic extract of the genus Aspergillus is immersed in water to obtain an aqueous solution of the genus Aspergillus. In a preferred specific embodiment, in step (b), an organic solvent layer and an aqueous layer are formed by distributing and extracting the Acerium aqueous solution obtained in step (b1) with the organic solvent, and then the aqueous layer is collected. do.

In another specific embodiment, the method for producing a Noriflora extract further comprises step (c) after step (b). In step (c), the aqueous layer obtained in step (b) is partitioned and extracted with 1-butanol to form a 1-butanol layer and an aqueous layer. Subsequently, the aqueous layer is collected to obtain the Noriflorum extract.

In a specific embodiment, the genus Sarcodia is Sarcodia ceylanica.

In another specific embodiment, the alcoholic solvent is ethanol. In a preferred embodiment, the alcoholic extract of the genus Aspergillus is an ethanolic extract of the genus Aspergillus.

In a specific embodiment, the organic solvent is ethyl acetate.

In the present invention, the extract of the genus Salmonella achieves the effect of skin whitening by inhibiting melanin production or reducing melanin. In a specific example, the Acerium extract inhibits melanin production or reduces melanin. In a preferred embodiment, the A. genus extract is used to prepare a composition that inhibits melanin production or reduces melanin. In a more preferred specific embodiment, the A. genus extract is used to produce a pharmaceutical or cosmetic product that inhibits melanin production or reduces melanin.

In specific embodiments, the composition includes a cosmetic material composition, a food additive, or a pharmaceutical composition. In preferred embodiments, the composition includes a cosmetic composition, a food product, or a drug. The composition can thus be used for producing cosmetics, foods or drugs. In another specific embodiment, the Trifolium extract is used to produce a pharmaceutical or cosmetic product for skin whitening.

In an exemplary embodiment, the composition can be a cosmetic composition. In addition to the Salmonella extract, the cosmetic composition may contain functional additives and ingredients commonly included in cosmetic compositions. Functional additives may include ingredients selected from water-soluble vitamins, fat-soluble vitamins, polypeptides, polysaccharides, sphingolipids, and seaweed extracts. In addition to these, oils, fats, humectants, emollients, surfactants, organic or inorganic pigments, organic powders, ultraviolet absorbers, preservatives, disinfectants, antioxidants, plant extracts, pH adjustment. The composition may further contain a pH control agent, alcohol, coloring agent, fragrance, blood circulation promoter, refreshing agent, antiperspirant, pure water, or the like.

The formulation of the cosmetic composition is not particularly limited and may be appropriately selected depending on the purpose. For example, skin lotion, emollient, skin toner, astringent, lotion, milk lotion, moisturizing lotion, nourishing lotion, etc. g lotion) , massage cream, nourishing cream, moisturizing cream, hand cream, foundation, essence, nourishing g essence), pack ( The cleaning product is composed of one or more of the following: pack, soap, cleansing foam, cleansing lotion, cleansing cream, body lotion, and body cleanser. (However, this is not limited to).

The present invention further provides a method of whitening skin by inhibiting or reducing melanin production. In the method, an effective dose of the composition is administered to the skin of an individual. The composition includes an extract of the genus Aspergillus, and the method for producing the extract of the genus Aspergillus includes the following steps. That is, (a) extracting the genus Aspergillus with an alcohol-based solvent to obtain an alcoholic extract of the genus Aspergillus. The alcoholic solvent is methanol or ethanol.

In a specific embodiment, the Acerium in step (a) is washed, dried and/or pulverized.

In another specific embodiment, the method for producing a Noriflora extract further comprises step (b) after step (a). In the step (b), an organic solvent layer and an aqueous layer are formed by distributing and extracting the alcoholic extract of the genus Salmonella using an organic solution or supercritical extraction. Subsequently, the aqueous layer is collected to obtain a Noriflora aqueous extract. The organic solution is an organic solvent or a mixture of water and an organic solvent. The organic solvent is ethyl acetate, propyl acetate, butyl acetate, hexane, heptane, octane, nonane, methyl ether, ethyl ether, dichloromethane, chloroform or carbon tetrachloride.

In a specific embodiment, the method for producing a Salmonella extract further includes step (b1) before the extraction with the organic solution. In the step (b1), the alcoholic extract of the genus Aspergillus is immersed in water to obtain an aqueous solution of the genus Aspergillus. In a preferred specific embodiment, in step (b), an organic solvent layer and an aqueous layer are formed by distributing and extracting the Acerium aqueous solution obtained in step (b1) with the organic solvent, and then the aqueous layer is collected. do.

In another specific embodiment, the method for producing a Noriflora extract further comprises step (c) after step (b). In step (c), the aqueous layer obtained in step (b) is partitioned and extracted with 1-butanol to form a 1-butanol layer and an aqueous layer. Subsequently, the aqueous layer is collected to obtain the Noriflorum extract.

In a specific embodiment, the genus Sarcodia is Sarcodia ceylanica.

In another specific embodiment, the alcoholic solvent is ethanol. In a preferred embodiment, the alcoholic extract of the genus Aspergillus is an ethanolic extract of the genus Aspergillus.

In a specific embodiment, the organic solvent is ethyl acetate.

In another specific embodiment, said individual is an animal, preferably a mammal, more preferably a human.

In the present invention, the composition is administered to the skin of the individual to suppress or reduce melanin in the skin area, thereby whitening the skin at the skin area. In specific embodiments, the composition is prepared in the form of an emulsion, lotion, serum, sunscreen, makeup base, or facial mask.

As used herein, the term "effective dose" refers to the amount that, under specified conditions, can prevent, reduce, arrest, or reverse the progression of symptoms in an individual, or that can A therapeutic dose capable of partially or completely alleviating the symptoms present under the circumstances. Those skilled in the art can easily determine the appropriate dosage and usage method for administering the A. genus extract to an individual. For example, the Acerium extract can be administered to the individual once or twice. Dosages and regimens include an understanding of the effective dosage of the Trifolium extract to be administered to the individual when administered multiple times, including the total amount of product administered during the entire duration of the dosage and regimen. It includes getting.

In the case of skin whitening, in a specific embodiment, the effective dosage range of the Acerium extract is from 5 μg/ml to 500 μg/ml. In a preferred embodiment, the effective dosage range of the Acerium extract is from 20 μg/ml to 200 μg/ml. In a more preferred specific embodiment, the effective dosage range of the Acerium extract is from 50 μg/ml to 100 μg/ml.

The invention further provides the use of the composition in the manufacture of a medicament for anti-inflammation. The composition includes an extract of the genus Aspergillus, and the method for producing the extract of the genus Aspergillus includes the following steps. That is, (a) extracting the genus Aspergillus with an alcohol-based solvent to obtain an alcoholic extract of the genus Aspergillus. The alcoholic solvent is methanol or ethanol.

In a specific embodiment, the Acerium in step (a) is washed, dried and/or pulverized.

In another specific embodiment, the method for producing a Noriflora extract further comprises step (b) after step (a). In the step (b), an organic solvent layer and an aqueous layer are formed by distributing and extracting the alcoholic extract of the genus Salmonella using an organic solution or supercritical extraction. Subsequently, the aqueous layer is collected to obtain a Noriflora aqueous extract. The organic solution is an organic solvent or a mixture of water and an organic solvent. The organic solvent is ethyl acetate, propyl acetate, butyl acetate, hexane, heptane, octane, nonane, methyl ether, ethyl ether, dichloromethane, chloroform or carbon tetrachloride.

In a specific embodiment, the method for producing a Salmonella extract further includes step (b1) before the extraction with the organic solution. In the step (b1), the alcoholic extract of the genus Aspergillus is immersed in water to obtain an aqueous solution of the genus Aspergillus. In a preferred specific embodiment, in step (b), an organic solvent layer and an aqueous layer are formed by distributing and extracting the Acerium aqueous solution obtained in step (b1) with the organic solvent, and then the aqueous layer is collected. do.

In another specific embodiment, the method for producing a Noriflora extract further comprises step (c) after step (b). In step (c), the aqueous layer obtained in step (b) is partitioned and extracted with 1-butanol to form a 1-butanol layer and an aqueous layer. Subsequently, the aqueous layer is collected to obtain the Noriflora extract.

In a specific embodiment, the genus Sarcodia is Sarcodia ceylanica.

As used herein, the term "anti-inflammatory" includes, but is not limited to, treating or treating inflammatory conditions.

In specific embodiments, the anti-inflammatory includes inhibition of inflammatory factors. In a preferred embodiment, the inflammatory factors include cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). In a more preferred specific embodiment, the Acerium extract suppresses inflammation caused by cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS).

In other words, the extract of the genus Salmonella can suppress inflammation and can further be applied to the treatment of allergic dermatitis. In a specific embodiment, the Acerium extract treats allergic dermatitis by being anti-inflammatory. In a preferred embodiment, the drug treats allergic dermatitis by being anti-inflammatory.

As used in this text, the term "treatment" refers to the alleviation of symptoms or complications, the delay in the progression of a disease, disease or condition, the reduction or alleviation of symptoms and complications, and/or the cure of a disease, disease or condition. or means removal.

The term "allergic dermatitis" as used in this text is a general term for skin diseases caused by allergic reactions, characterized by chronic itching and rashes on the face, neck, elbows and/or knees. shall be. Examples of allergic dermatitis include contact dermatitis and atopic dermatitis. "Contact dermatitis" is an eczematous inflammatory disease that develops when foreign antigens come into contact with the skin, such as allergic contact dermatitis, photocontact dermatitis, systemic contact dermatitis, and contact dermatitis. Examples include urticaria. Examples of antigens include metal allergens (cobalt, nickel, etc.), plant allergens (sumac, primrose, etc.), and food allergens (mango, ginkgo, etc.). "Atopic dermatitis (AD)" refers to a skin disease in which many patients have an atopic tendency. It is also characterized by symmetrical systemic eczema that repeatedly worsens and eases, such as diffuse neurodermatitis, atopic eczema, atopic neurodermatitis, Besnier prurigo, acute infantile eczema, flexural eczema, Examples include pediatric eczema of the extremities, atopic eczema in children, eczema dry in children, eczema in children, atopic dermatitis in adults, endogenous eczema, dermatitis in children, and chronic eczema in children.

In specific embodiments, the allergic dermatitis includes contact dermatitis or atopic dermatitis. In a preferred embodiment, the allergic dermatitis includes atopic dermatitis. In a more preferred specific example, the atopic dermatitis includes diffuse neurodermatitis, atopic eczema, atopic neurodermatitis, prurigo beignet, acute infantile eczema, flexural eczema, extremity pediatric eczema, and pediatric atopic dermatitis. Includes eczema, childhood dry eczema, childhood eczema, adult atopic dermatitis, endogenous eczema, childhood dermatitis or chronic childhood eczema.

In another specific example, the drug suppresses symptoms of atopic dermatitis, including erythema, edema, epidermal peeling, or skin dryness.

In a specific example, the drug reduces the increase in IgE expression level resulting from the atopic dermatitis.

In another specific example, the drug ameliorates spleen or lymph node enlargement resulting from the atopic dermatitis.

In a specific embodiment, the drug further comprises a pharmaceutically acceptable carrier. The term "pharmaceutically acceptable carrier" as used herein is determined by the particular combination and composition to be applied in the particular manner. As used herein, the term "carrier" includes any and all solvents, dispersion media, excipients, coatings, diluents, penetration and absorption delaying agents such as antibacterial and antifungal agents, buffers, etc. Examples include (but are not limited to) agents, carrier solutions, suspensions, colloids, and the like. These media and reagents used for drug active substances are known in the art. Unless there is an incompatibility between the active ingredients and any common media or reagents, therapeutic combinations should be considered. Supplementary active ingredients may also be incorporated into the compositions. The term "pharmaceutically acceptable" refers to the absence of allergic or similar side reactions when the molecular entities and compositions are applied to a subject. The production of water compositions with proteins as active substances is well known in the art. Usually, the composition is manufactured as a liquid/solution, tablet, capsule or suspension injection. It may also be prepared as a dissolvable solid or a suspension solid that can be used as an injection. In another specific embodiment, the pharmaceutically acceptable carrier includes a dermatologically acceptable medium. By "dermatologically acceptable medium" is meant biologically relevant substances such as, for example, salts, esters and/or acid amide components. That is, the substance, when used in conjunction with the selected active ingredients, does not cause undesired biological effects when administered to an individual. Further, the substance is a substance that does not cause any harmful interaction with any component of the drug component containing this substance. Similarly, "dermatologically acceptable salts" or "dermatologically acceptable esters" in the context are biologically appropriate salts or esters.

In the present invention, the formulation of the composition (containing the Trifolium extract) and a pharmaceutically acceptable carrier includes a sterile aqueous solution or dispersion, an aqueous suspension, an oil emulsion, water in oil emulsion, Point emulsions, long-duration emulsions, viscous emulsions, microemulsions, nanoemulsions, liposomes, microparticles, microspheres, nanospheres, nanoparticles, micromercury, and several types of sustained release natural or synthetic polymers are available. be. The pharmaceutically acceptable carrier and the Acerium extract are used to deliver aerosols, tablets, pills, capsules, sterile powders, suppositories, detergents, creams, ointments, pastes, gels, hydrogels, or compositions. It may also be formulated in other possible formulations.

Furthermore, the compositions referred to in the present invention include compositions that are administered locally and regionally to act. As used herein, the term "topical" refers to the use of the compositions described in the text, mixed with a suitable medicinal carrier, and applied to areas of the skin (e.g., areas affected by allergic dermatitis). Relates to exerting local effects. Such topical compositions therefore include drug forms such as compounds that are applied externally in direct contact with the surface of the skin to be treated. Common drug forms for this purpose include ointments, rubs, creams, shampoos, emulsions, pastes, gels, sprays, aerosols, and the like. It can also be used in the form of a patch or a wet bandage, depending on the body part to be treated. The term "ointment" includes formulations (including creams) having an oily base, a water-soluble base, and an emulsion base. The substrate is, for example, petrolatum, lanolin, polyethylene glycols, and mixtures of combinations thereof.

The medicaments of the invention further include pharmaceutically acceptable carriers and can be administered to an individual in a number of different ways, by therapeutic modalities well known in the art to which the invention pertains. In some embodiments, the composition (including the A. spp. extract) and a pharmaceutically acceptable carrier are administered topically, intravenously, intramuscularly, subcutaneously, topically, orally, or by inhalation. The drug is also delivered to the target site by the digestive and circulatory systems.

In another specific embodiment, said individual is an animal, preferably a mammal, more preferably a human.

In the case of anti-inflammation, in a specific embodiment, the effective dosage range of the Acerium extract is from 1 mg/kg body weight to 200 mg/kg body weight. In a preferred embodiment, the effective dosage range of the Acerium extract is from 5 mg/kg to 100 mg/kg body weight. In a more preferred specific embodiment, the effective dosage range of the Acerium extract is from 10 mg/kg to 40 mg/kg body weight.

When treating allergic dermatitis, in a specific embodiment, the effective dosage range of the Acerium extract is from 0.05 to 20 mg/ml. In a preferred embodiment, the effective dosage range of the Acerium extract is from 0.1 to 10 mg/ml. In a more preferred specific embodiment, the effective dosage range of the Acerium extract is from 0.5 to 2 mg/ml.

FIG. 1 shows the extraction flow for the genus Acerium. FIG. 2 shows the effect of Noriflorum extract EH on intracellular melanin content. FIG. 3 shows the influence of Noriflorum extract EH on the fish body pigment of zebrafish. Nine hours after fertilization, the zebrafish embryo body was administered with the extract EH of the genus Trifolium, and after being immersed for 48 hours, the larvae were taken out, and the fish bodies were photographed and analyzed. In addition, 5.4 mg/mL arbutin and 30.4 μg/mL PTU were used as a positive control group. The abdomen of the fish was marked using image quantification software, and the expression level of melanin production in each group of zebrafish was analyzed. The results showed that EH (100 μg/mL) can suppress melanin production in zebrafish and has whitening activity. Data represent mean ± standard error of the mean (mean ± SEM). In addition, * indicates a significant difference (P<0.05) compared to the control group. FIG. 4 shows the effect of Noriflorum extract EH on lipopolysaccharide (LPS)-induced iNOS. An inflammatory response was induced in Raw264.7 cells with 10 ng/mL of lipopolysaccharide, and 20 μg/mL, 50 μg/mL, and 100 μg/mL of Attica extract EH were added and cultured for 16 hours. In addition, 10 μM dexamethasone (Dex) was used as a positive control group. Analysis of the expression level of the inflammatory factor iNOS by Western blotting showed that EH can significantly suppress iNOS. Data represent mean ± standard error of the mean (mean ± SEM). In addition, * indicates a significant difference (P<0.05) compared to the LPS group. FIG. 5 shows the effect of Noriflorum extract EH on lipopolysaccharide (LPS)-induced COX-2. An inflammatory response was induced in Raw264.7 cells with 10 ng/mL of lipopolysaccharide, and 20 μg/mL, 50 μg/mL, and 100 μg/mL of Attica extract EH were added and cultured for 16 hours. In addition, 10 μM dexamethasone (Dex) was used as a positive control group. Analysis of the expression level of the inflammatory factor COX-2 by Western blotting showed that EH can significantly suppress COX-2. Data represent mean ± standard error of the mean (mean ± SEM). In addition, * indicates a significant difference (P<0.05) compared to the LPS group. FIG. 6 shows the effect of Nordicum extract EH on the skin appearance of mice suffering from atopic dermatitis. (A) in the figure shows atopic dermatitis induced with DNCB, and after symptoms of atopic dermatitis appear on the skin of mice, daily drug application is started, and on the 1st and 7th days of treatment. , shows the skin appearance of mice with DNCB-induced atopic dermatitis taken on day 12. Note that the scale bar is 1 cm. As a result, compared to the AD group, both the EHL group (low dose group) and the EHH group (high dose group) had the effect of moderating the symptoms of atopic dermatitis, and the epidermis. Phenomena such as edema, redness, dryness and crusting were all alleviated. (B) in the figure shows the clinical dermatitis score for alleviation of atopic dermatitis symptoms by Noriflorum extract EH on the 12th day of treatment. The alleviation of atopic dermatitis symptoms due to EH was evaluated using a clinical dermatitis score. At this time, the severity of dermatitis was evaluated using four skin surface symptoms: erythema/bleeding, edema, epidermal peeling/erosion, and dryness. Each symptom was given a score of 0 to 3 depending on its severity, and the higher the score, the more severe the symptoms. The total score for dermatitis was the sum of the above four types of scores, with a maximum of 12 points. The higher the score, the more severe the dermatitis. Data represent mean ± standard error of the mean (mean ± SEM). Also, those that had a significant difference compared to the AD group (P<0.05) are indicated by *, and those that had a significant difference compared to the ADV group are indicated by #. FIG. 7 shows the influence of Nordicum extract EH on serum IgE. Before killing the animals, blood was collected and IgE in the serum was detected. IgE increased due to DNCB-induced atopic dermatitis, but IgE decreased by applying Noriflorum extract EH. Data represent mean ± standard error of the mean (mean ± SEM). Also, those that had a significant difference compared to the AD group (P<0.05) are indicated by *, and those that had a significant difference compared to the ADV group are indicated by #. Figure 8 shows the effect of Noriflorum extract EH on DNCB-induced enlarged spleen weight. Spleen tissues were collected at the time of animal sacrifice, photographed, and weighed. Although the spleen tissue was swollen due to DNCB-induced atopic dermatitis, the weight of the spleen was reduced by applying Noriflorum extract EH. Note that the scale bar is 1 cm. Data represent mean ± standard error of the mean (mean ± SEM). Also, those that had a significant difference compared to the AD group (P<0.05) are indicated by *, and those that had a significant difference compared to the ADV group are indicated by #. Figure 9 shows the effect of Noriflorum extract EH on DNCB-induced enlarged lymph node weight. Lymph node tissue was collected, photographed, and weighed at the time of animal sacrifice. The lymph node tissue was swollen due to DNCB-induced atopic dermatitis, but the weight of the lymph node was reduced by applying Noriflorum extract EH. Note that the scale bar is 0.5 cm. Data represent mean ± standard error of the mean (mean ± SEM). Also, those that had a significant difference compared to the AD group (P<0.05) are indicated by *, and those that had a significant difference compared to the ADV group are indicated by #.

Extraction of cultivated Sarcodia ceylanica In the present invention, artificially cultivated Sarcodia ceylanica was used.

Dried Noriflorum was obtained by drying it under conditions of 50° C. for 24 hours. 10.8 kg of dried Acerium was ground, filtered through a 50 mesh filter, and then extracted three times by soaking in 95% alcohol (EtOH) at room temperature. Then, by filtering the three immersion liquids together and concentrating them under reduced pressure, 370.5 g of a crude alcoholic extract of the genus Agaricus was able to be obtained. Next, the above-mentioned crude extract of the genus Attica was added to 1 L of water to form a suspension, and then 1 L of ethyl acetate (EtOAc) was added to perform partition extraction. The above partition extraction was repeated three times to form an ethyl acetate layer and an aqueous layer, and after removing the ethyl acetate layer, the aqueous layer was collected. Further, the aqueous layer was subjected to partition extraction with 1 L of 1-butanol (n-BuOH), and the above partition extraction was repeated three times to form a 1-butanol layer and an aqueous layer. Then, the 1-butanol layer was removed, and the separated aqueous layer was filtered through a C18 glass column to remove excess salts, and then dried to obtain extract EH (150 g). Figure 1 shows the entire extraction flow for the genus Acerium.

Further, in the above extraction step, the alcohol solution may be replaced with a methanol solution. Additionally, the step of extracting with ethyl acetate may be replaced with other organic solvents. For example, partition extraction using propyl acetate, butyl acetate, hexane, heptane, octane, nonane, methyl ether, ethyl ether, dichloromethane, chloroform or carbon tetrachloride solvents or supercritical extraction (e.g. supercritical CO ₂ extraction) After that, it is also possible to obtain an extract with the same components as EH by extracting with 1-butanol.

Alternatively, water may be mixed with ethyl acetate or other organic solvent to form an organic solution, and the alcoholic crude extract of the genus Aspergillus may be directly extracted. In this case, it is not necessary to separately extract water and organic solvent in two steps. In addition, the alcoholic crude extract of the genus Aspergillus may be extracted using ethyl acetate or other organic solvent as is, without requiring the step of immersing it in water in advance. Even by changing the above steps, it is possible to finally obtain an extract with the same components as EH.

The above supercritical CO ₂ extraction conditions are a flow rate ratio of CO ₂ :95% ethanol solution=10 mL/min:1 mL/min, a critical pressure of 250 bar, and a critical temperature of 40°C. Supercritical CO ₂ extraction similarly separates the raw material (aqueous layer) remaining in the supercritical CO ₂ extraction reactor and the substance to be extracted. Therefore, by extracting the raw material (aqueous layer) in the supercritical CO ₂ extraction reaction tank with 1-butanol, the Acerium extract EH is obtained.

Moreover, in the present invention, the polysaccharide content of EH was measured by the phenol-sulfuric acid method, and as a result, EH did not contain any polysaccharide components. Therefore, the polysaccharide component was not eluted by the extraction method in which the genus Aspergillus was immersed in alcohol in advance, and the alcoholic crude extract of the genus Aspergillus contained no polysaccharide component.

Experimental method (1) Evaluation of the whitening effect of EH (a) In vitro cell test B16-F10 cells were cultured in the wells of a 24-well culture plate at a density of 10 ⁴ cells per well and placed in a cell incubator. After 24 hours, the original cell culture medium was removed, and a cell culture medium containing a Noriflora extract was added, and then placed in the incubator again and cultured for 48 hours. Next, cells were collected using the action of trypsin, washed with phosphate buffered saline (PBS), and then 100 μl of 1N NaOH aqueous solution was added and reacted at 90° C. for 1 hour. Then, the absorbance value at a wavelength of 405 nm was detected using an enzyme immunoanalyzer, and data analysis was performed. By setting the data of the control group as 100% and comparing the strengths and weaknesses of the light absorption values between the experimental groups, the whitening effect of Noriflorum extract EH was shown. In addition, arbutin and N-phenylthiourea (PTU), which are used for skin whitening, were used as a positive control group. Additionally, α-Melanocyte-stimulating hormone (α-MSH) was used to promote melanin production in cells.

(b) Analysis of whitening activity of living zebrafish In the experiment, zebrafish (AB strain Danio rerio) aged 4 months or more were used and cultured for the experiment. Zebrafish were kept in acrylic tanks equipped with filters and circulation systems, and the water temperature was controlled at 28.5°C. Furthermore, the light and dark cycles were controlled to be 14 hours and 10 hours, respectively.

The zebrafish embryo body was collected 9 hours after fertilization and injected into a 96-well plate. Three embryo bodies and 100 μL of Hank's buffer (0.04 mM NaHCO ₃ , 1.3 mM CaCl ₂ , 2 mM MgSO ₄ ) were present in each well. Next, 100 μL of 1% dimethyl sulfoxide (DMSO) was added to the control group, and 100 μL of 5.4 mg/mL arbutin (Arbutin, Sigma-Aldrich, Missouri, USA) was added to the positive control group and experimental group, respectively. , Cat. No. #A4256), 30.4 μg/mL of N-phenylthiourea (PTU, Sigma-Aldrich, Missouri, USA, Cat. No. #P7629), and concentrations of 50 μg/mL, 100 μg /mL and 200 μg/mL of Noriflorum extract EH (both dissolved in 1% DMSO) were added and placed in a temperature-controlled lighted incubator (light/dark cycle: 14/10 hours, 28.5 °C). Cultured for 48 hours. Forty-eight hours after the drug treatment (ie, 57 hours after fertilization), the young fish were anesthetized with the anesthetic Tricaine (168 ppm, MS-222) and placed in the groove of a whole slide glass. The fish bodies were then fixed with 2% methyl cellulose (Sigma-Aldrich, Missouri, USA, Cat. No. #M0512) and observed with a stereomicroscope (Z16 APO, Leica, Heerbruck, Switzerland). In addition, fish body images were obtained using a combination of an image capture system and software (idea SPOT & SPOT software VERSION 4.6, Diagnostic Instruments Inc., USA). Using image processing software (Image J, National Institutes of Health, Maryland, USA) for the fish images, the area of the fish abdomen was marked, and the melanin values of the zebrafish in each group were quantitatively analyzed. Then, by comparing the melanin values of the experimental group with the melanin value of the control group set as 100%, the whitening effect of Noriflorum extract EH was evaluated.

(2) Evaluation of anti-inflammatory activity of EH In vitro cell test 5 × 10 ⁵ Raw264.7 cells were transplanted into a 6 cm petri dish, and after adhering, lipopolysaccharide (LPS) (0.01 μg/mL, Sigma-Aldrich Inc., Missouri, USA, Cat. No. #L2654). After 10 minutes, different concentrations of EH were added, and 10 μM Dexamethasone (Dex) (Sigma-Aldrich, Missouri, USA, Cat. No. #D4902) was used as a positive control group, and the cells were cultured for 16 hours. Next, the anti-inflammatory activity of EH was evaluated by Western blotting, and cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (COX-2), which are proteins involved in inflammation promotion, were evaluated. The relative expression level of oxide synthase, iNOS) was analyzed. Furthermore, the group to which lipopolysaccharide (LPS) was added alone was set as 100%. Finally, β-actin was used as an endogenous control group.

(3) Therapeutic effect of EH on atopic dermatitis The experimental animals used in the present invention were BALB/c strain mice. After the mouse was anesthetized with 2.5% isoflurane, the hair on the back of the mouse was removed using a shaver and hair removal cream, and marked with a 1 cm diameter silicone rubber (area 78.5 mm ² ). Next, once every two days, 26 μL of 2% 2,4-dinitrochlorobenzene (DNCB) (Sigma-Aldrich, Missouri, USA, Cat. No. #138630) was dropped into the above range. did. This was done a total of 8 times to induce skin lesions.

Seven days after DNCB induction, 100 μL of Vehicle, Noriflorum extract EH, or the atopic dermatitis treatment crisaborole were applied daily. Experimental animals were: (1) control group: uninduced, (2) AD group: administered only 2% DNCB, (3) ADV group: administered 2% DNCB and vehicle, (4) EHL group: 50 μg EH/100 μL of 1% methylcellulose was administered after DNCB induction, (5) EHH group: 200 μg EH/100 μL of 1% methylcellulose was administered after DNCB induction, and (6) Cri group: 25 μg crisabolol/1% after DNCB induction. 100 μL of acetone-EtOH was administered and the animals were divided into groups (3 animals in each group). Further, 5 minutes after applying the DNCB, the medicine was applied after waiting for the DNCB to dry. Before induction or drug application, changes in skin symptoms were photographed and recorded with a digital camera.

On the 18th day, the animals were sacrificed and blood was collected, as well as dorsal skin, spleen, and lymph node tissues. Then, the sizes of the spleen and subiliac lymph nodes were observed, weighed, and compared. In addition, the severity of clinical dermatitis was evaluated based on four symptoms: erythema/hemorrhage, edema, excoriation/erosion, and dryness on the skin surface. . A score of 0 to 3 was given depending on the severity of each symptom, with 0 being no symptoms, 1 being mild, 2 being moderate, and 3 being severe. The total score for dermatitis was the sum of the above four types of scores, with a maximum of 12 points. The higher the score, the more severe the dermatitis.

Before sacrifice, the blood of the mice was collected by cardiac bleeding into blood collection tubes (BD vacutainer-SST, New Jersey, USA). Thereafter, the blood was centrifuged at 3000 rpm for 10 minutes to obtain serum. Serum was stored in a -80°C refrigerator until further use. The IgE concentration in the serum was then detected according to the manufacturer's instructions (IgE-ELISA kit, Thermo Fisher Scientific, Vienna, Austria).

When inflammation or immune-related diseases occur, the lymph nodes and spleen swell. Therefore, when the mice were sacrificed, these two organs were collected, photographed, and weighed.

Statistical analysis All experimental data are expressed as mean ± standard error of the mean (mean ± SEM). Statistical analysis of the data was performed by one-way analysis of variance (ANOVA) to compare data between multiple groups. In addition, multiple comparisons were made for differences between groups using Duncan's Method. In addition, when the P value was smaller than 0.05, it was determined that there was a significant difference between the groups.

Results (1) Whitening effect of EH Melanin production was induced in B16F10 cells using 100 mM α-MSH, and 10 μg/ml EH solution or 100 μM PTU was administered and cultured for 48 hours. Thereafter, cells were collected and melanin was dissolved with 1N NaOH. Finally, the absorbance value at a wavelength of 405 nm was read. The more melanin there was, the higher the absorbance value was. The results are as shown in Figure 2. PTU of the control group was 100 ± 5.33% and PTU of the positive control group was 37.41 ± 3.94%, whereas 10 μg/mL of EH significantly reduced cellular melanin production. (72.64±2.79).

The whitening activity of EH was evaluated using an environmental administration method. 48 hours after administering the drug to the zebrafish embryo body, the fish body pigments of the larval fish were photographed and the pigment spots were quantitatively analyzed. The results were as shown in Figure 3. The control group was 100±6.06%, and both arbutin and PTU in the positive control group significantly suppressed fish body pigment (9.86±1.40%, 3.08±0.62%). On the other hand, EH of 50 μg/mL, 100 μg/mL, and 200 μg/mL was able to significantly suppress fish body pigment (78.61 ± 7.68%, 70.12 ± 8.62%, 63.64 ± 8 .50%).

(2) Anti-inflammatory effect of EH It was examined whether EH has the effect of suppressing inflammatory reactions. LPS was added to Raw264.7 cells to induce an inflammatory response, and EH at concentrations of 20 μg/mL, 50 μg/mL, and 100 μg/mL were added and cultured together for 16 hours. Thereafter, the expression levels of the inflammatory proteins iNOS and COX-2 were detected by Western blotting. The results were as shown in FIG. In the control group, LPS did not induce an inflammatory response, so the expression level of iNOS was 1.04±0.15%. In contrast, the iNOS expression level in the LPS group was 100.00±10.74%. On the other hand, when dexamethasone (Dex) at a concentration of 10 μM was used as a positive control group, the expression level of iNOS in this group was significantly reduced (14.78±0.92%). Furthermore, 100 μg/mL of EH was able to significantly suppress the expression level of iNOS (65.95±1.95%).

As shown in FIG. 5, in the control group, LPS did not induce an inflammatory response, so the expression level of COX-2 was 4.65±3.12%. In contrast, the expression level of COX-2 in the LPS group was 100.00±0.99%. On the other hand, when dexamethasone (Dex) at a concentration of 10 μM was used as a positive control group, the expression level of COX-2 was significantly suppressed (2.90±0.71%). In addition, EH of 20 to 100 μg/mL can significantly suppress COX-2, and the expression levels are 68.55 ± 0.46%, 35.43 ± 9.55%, and 72.77 ± 7.81, respectively. %.

(3) Therapeutic effect of EH on atopic dermatitis Symptoms of DNCB-induced atopic dermatitis (AD) in mice included phenomena such as erythema, edema, epidermal detachment, dryness, and lichenification. . After the mice showed obvious symptoms such as erythema, edema, epidermal exfoliation, and dryness, EH or crisaborole (Cri) was applied daily to test whether EH has a therapeutic effect on AD. As shown in FIG. 6A, the skin appearance symptoms of the mice were observed, photographed, and recorded, and as shown in FIG. 6B, the therapeutic effect of EH was quantified using a clinical dermatitis score.

In the control group, the skin surface was dry due to less fur, and the score was 0.75±0.25. Corneocytes proliferated on the skin surface of the AD group and the ADV group, and a thick scab was formed. As the days passed, some of the scabs peeled off, and dryness of the skin around the induced skin was observed. In addition, wrinkles were observed on the skin. In addition, erythema and edema appeared on the skin due to inflammation. However, as corneocytes continued to proliferate, scabs also appeared on the skin surface. The clinical dermatitis scores of these two groups were significantly increased compared to the control group, being 9.17±0.40 and 9.50±0.56, respectively. On the other hand, in the group to which EH and crisabolol were applied day by day, dryness, erythema, and edema were observed after the scabs were peeled off, but the degree of proliferation of keratinocytes seemed to be smaller than in the AD group. Therefore, before sacrificing the animals, the dermatitis scores of the EHL and EHH groups were significantly reduced (4.50±0.50 and 3.67±0.67). On the other hand, the dermatitis score of the Cri group was 4.80±0.37, which was statistically significant compared to the AD group. The above results indicate that EH has the effect of alleviating AD symptoms.

IgE is one of the clinical diagnostic indicators for atopic dermatitis. Before killing the mice, serum was collected and the content of IgE was measured, and the results were as shown in FIG. 7. The serum IgE content of the control group was 1.71±0.14 μg/mL. Furthermore, the IgE concentrations in the AD group and ADV group were clearly elevated (68.89±4.12 μg/mL and 68.95±2.60 μg/mL). On the other hand, the IgE content in the EHL group and the EHH group significantly decreased to 52.32±3.41 μg/mL and 46.31±3.81 μg/mL. On the other hand, the serum IgE content of the Cri group decreased to 65.61±1.74 μg/mL. Serum IgE, which increased due to atopic dermatitis, could be lowered by applying EH.

When inflammation or immune-related diseases occur, the lymph nodes and spleen swell. Therefore, when the mice were sacrificed, these two organs were collected, photographed, and weighed. The results of spleen weight were as shown in FIG. The spleen weight of the control group was 91.08±3.61 mg. Furthermore, the spleens of the AD group and ADV group were clearly swollen, and were 2.5 times larger than those of the control group (234.46±6.56 mg and 221.14±13.32 mg). In contrast, the spleen weights of the EHL and EHH groups were significantly reduced (161.23±9.97 mg and 171.07±5.58 mg). On the other hand, the spleen weight of the Cri group was significantly reduced to 167.46±10.61 mg.

The results of the total weight of lymph nodes were as shown in FIG. The total weight of the two lymph nodes in the control group was 4.46±0.29 mg. In addition, the lymph nodes in the AD group and ADV group were clearly swollen, three times as large as those in the control group (12.07±0.33 mg and 11.61±0.54 mg). In contrast, the lymph node weights of the EHL and EHH groups were significantly reduced (9.06±0.54 mg and 9.13±0.75 mg). On the other hand, the lymph node weight in the Cri group was significantly reduced to 9.49±0.81 mg. From the above results, it was possible to suppress the above phenomenon by applying EH to the lymph nodes and spleen that were swollen due to inflammation or immune reaction due to atopic dermatitis.

It is properly stated that the invention may be practiced with requirements or limitations not specifically disclosed herein. The terminology used for description is not intended to be limiting. Although there is no difference in the expressions and descriptions using these terms and any other equivalents, it should be recognized that the rights in the present invention are subject to modification. Therefore, although embodiments and other situations have been described in the present invention, the contents disclosed in the main text can be supplemented and modified by those skilled in the art, and such modifications and variations are within the scope of the rights of the present invention. It is considered that

Claims (11)

A method for producing a Noriflorum extract, comprising:
(a) extracting the genus Aspergillus with an alcohol-based solvent to obtain an alcohol-based extract of the genus Aspergillus, the alcohol-based solvent being methanol or ethanol;
(b) After forming an organic solvent layer and an aqueous layer by distributing and extracting the alcoholic extract of the genus Attica using an organic solution or supercritical extraction, the aqueous layer is collected; and an organic solvent, the organic solvent being ethyl acetate, propyl acetate, butyl acetate, hexane, heptane, octane, nonane, methyl ether, ethyl ether, dichloromethane, chloroform or carbon tetrachloride,
(c) Partitionally extracting the aqueous layer obtained in step (b) with 1-butanol to form a 1-butanol layer and an aqueous layer, and then collecting the aqueous layer to obtain the A. genus extract. A manufacturing method comprising the steps of obtaining. The manufacturing method according to claim 1, wherein the alcohol solvent is ethanol. The manufacturing method according to claim 1, wherein the organic solvent is ethyl acetate. Use of a Noriflora extract obtained by the production method according to claim 1,
The extract of the genus Aspergillus is used in the preparation of a composition for skin whitening. 5. The use according to claim 4, wherein the Acerium extract inhibits melanin production or reduces melanin. 5. The use according to claim 4, wherein the composition includes a cosmetic composition, a food product or a drug. 2. Use of a Noriflora extract obtained by the production method according to claim 1, wherein the extract is used in the production of a drug for anti-inflammation. 8. The use according to claim 7, wherein said anti-inflammatory includes suppression of inflammatory factors. The use according to claim 8, wherein the inflammatory factors include cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Use of a Noriflora extract obtained by the production method according to claim 1,
The use of the Acerium extract in the manufacture of drugs for anti-inflammation,
8. The use according to claim 7, wherein the drug treats allergic dermatitis by being anti-inflammatory. Use of a Noriflora extract obtained by the production method according to claim 1,
The use of the Acerium extract in the manufacture of drugs for anti-inflammation,
8. The use according to claim 7, wherein the drug treats allergic dermatitis by anti-inflammation.
11. The use according to claim 10, wherein the allergic dermatitis includes atopic dermatitis.