KR102157755B1 - Composition for anti-inflammatory or anti-atopic containing Uncarina stellulifera extracts - Google Patents

Abstract

The present invention relates to an Uncarina stelulifera extract and a composition comprising the same as an active ingredient, and the composition comprising the Uncarina stelulifera extract as an active ingredient has excellent inflammatory cytokine and nitric oxide inhibitory activity, and TARC Because it has excellent inhibitory ability, it can be usefully used as an anti-inflammatory or anti-atopy food, pharmaceutical, and cosmetic composition.

Description

Anti-inflammatory or anti-atopic composition containing Uncarina stelulifera extract as an active ingredient {Composition for anti-inflammatory or anti-atopic containing Uncarina stellulifera extracts}

The present invention is Uncarina Stellurifera It is to provide an anti-inflammatory or anti-atopic composition comprising the extract as an active ingredient.

The inflammatory response is part of the innate immune response, and, as in other animals, the innate immune response in humans begins when macrophages recognize and attack as non-self through patterns on the cell surface that are specific to the pathogen. During an inflammatory reaction, plasma accumulates in the inflamed area, diluting the toxicity secreted by bacteria, increasing blood flow, and accompanying symptoms such as erythema, pain, swelling, and fever.

The inflammatory response in the skin begins as an action to protect against skin damage caused by physical stimulation, chemical substances, bacteria, etc., and various immune cells and inflammation-inducing cytokines are involved. IL-6 (interleukin-6), IL-8 (interleukin-8), IL-1β (interleukin-β), etc. are typical inflammation-inducing cytokines.

For example, IL-8 expression is induced in various cells such as peripheral blood monocytes, tissue macrophages, NK cells, fibroblasts, and vascular endothelial cells in response to stimulation by inflammatory cytokines. Inflammatory diseases related to elevated (eg, excessive) IL-8 levels include inflammatory skin diseases such as inflammatory keratosis (eg dry ringworm), atopic dermatitis, contact dermatitis, and the like.

Atopic dermatitis (AD) is an inflammatory skin disease accompanied by itching, which is chronic and usually begins in infancy. Atopic dermatitis is characterized by constant itching as its main symptom, and repeats recovery and deterioration for no specific reason. Despite recent studies on atopic dermatitis, the cause of atopic dermatitis has not been clearly identified, and various treatments are being developed, but interest in natural materials that can reduce skin irritation is increasing.

In accordance with this trend, natural materials in Madagascar were studied to obtain new natural raw materials. Madagascar is a clean area located in the Indian Ocean in the southeast of Africa, and is known as a country rich in natural resources, such as'Mysterious Island Country' and'Treasure Island'. The plant called Centella asiatica, which is the main ingredient of Dongkuk Pharm's signature wound treatment drug'Madekasol', is mainly produced in Madagascar. It is said that the brand name Madekasol is also derived from the place name of'Madagascar'. According to a report from the World Wildlife Fund (WWF), 80% of Madagascar's flora and fauna are known to be endemic species that cannot be found elsewhere.

Uncarina sp. , one of the native plant species of Madagascar, is a plant belonging to the Pedaliaceae family. It is mainly native to Madagascar in eastern Africa, but is not native to the country by examining new native plant species other than the known endemic species . It was identified as not.

Fortune also known as Carina ln belonging to 11 species, cloud Karina Gran non Didier Elie (U. grandidieri) and Karina lucky to Carry (U. decaryi) and paper etc., in other areas not native to Madagascar, research has not been conducted almost Actually.

Accordingly, the present inventors evaluate the possibility of a skin beauty material using Uncarina Stellurifera, a plant of the genus Uncarina, and intend to use it as basic data in the industrial field such as use as a cosmetic and food raw material.

(0001) Korean registered patent KR 10-1661688 (0002) Korean Patent Publication KR 10-2018-0065001

Therefore, the present invention is Uncarina Stelulipera ( Uncarina stellulifera ) is to provide an anti-inflammatory or anti-atopic composition comprising the extract as an active ingredient.

In order to achieve the above object, the present invention provides an extract of Uncarina stellulifera having an anti-inflammatory or anti-atopic effect.

In one embodiment, the extract may be extracted with water, alcohol, ethyl acetate, acetone, nucleic acid, dichloromethane, or a mixed solvent thereof.

According to another aspect of the present invention, the present invention provides an anti-inflammatory or anti-atopic composition comprising an extract of Uncarina stellulifera as an active ingredient.

In one embodiment, the composition may be extracted with water, alcohol, ethyl acetate, acetone, nucleic acid, dichloromethane, or a mixed solvent thereof.

According to another aspect of the present invention, the present invention provides an anti-inflammatory or anti-atopic cosmetic composition comprising an extract of Uncarina stelulifera as an active ingredient.

In one embodiment, the cosmetic composition is a soft lotion, gel, water-soluble liquid, milk lotion, nourishing cream, massage cream, essence, oil-in-water emulsion, water-in-oil emulsion, face anhydrous product, solid anhydrous Product, oil dispersion in aqueous phase using globules, ionic lipid vesicles, nonionic lipid vesicles, ointment, cleansing foam, cleansing water, pack, body oil, oil-in-water makeup base, water-in-oil makeup base, foundation, skin cover , Lipstick, lip gloss, face powder, two-way cake, eye shadow, mascara, cheek color, and eyebrow pencil can be formulated as one selected from the group consisting of.

According to another aspect of the present invention, the present invention provides an anti-inflammatory or anti-atopic pharmaceutical composition comprising Uncarina stelulipera extract as an active ingredient.

According to another aspect of the present invention, the present invention provides a health food composition for preventing or improving inflammation and atopy, including an extract of Uncarina stelulifera as an active ingredient.

According to another aspect of the present invention, the present invention provides an anti-inflammatory or anti-atopy quasi-drug composition comprising an extract of Uncarina stelulipera as an active ingredient.

The composition comprising the extract of Uncarina stelulifera of the present invention as an active ingredient has excellent anti-inflammatory or anti-atopic activity, so it can be usefully used as a food or cosmetic composition for preventing, alleviating or treating inflammation and preventing, alleviating or treating atopy. have.

1 is a schematic diagram showing a process for preparing an Uncarina stelulipera extract.
Figure 2 is a graph showing the cytotoxicity of the extract of Uncarina stelulipera to macrophages.
3 is a graph showing the IL-1β inhibitory activity of Uncarina stelulifera extract.
4 is a graph showing the IL-6 inhibitory activity of Uncarina stelulipera extract.
5 is a graph showing the TNF-α inhibitory activity of Uncarina stelulifera extract.
6 is a graph showing the Nitric oxide inhibitory activity of Uncarina stelulipera extract.
7 is a graph showing HaCaT cytotoxicity of Uncarina stelulifera extract.
8 is a graph showing the TARC inhibitory activity of Uncarina stelulifera extract.

The present invention is characterized by providing an anti-inflammatory or anti-atopic composition comprising an Uncarina stellulifera extract and an Uncarina stelulifera extract as an active ingredient having an anti-inflammatory or anti-atopic effect.

Uncarina steluipera of the present invention ( Uncarina stellulifera ) is one of the native plant species of Madagascar, belongs to the Pedaliaceae family, and is mainly native to Madagascar in eastern Africa. It is known that 11 species belong to the genus Uncarina , and there are species such as Uncarina grandidieri ( U. grandidieri ) and Uncarina dekari ( U. decaryi ), and they do not grow naturally outside Madagascar.

Until now, such uncarina stelulifera has not been reported on anti-inflammatory or anti-atopy studies.

The present inventors prepared an Uncarina stelulifera extract as a material of the composition, and the Uncarina stelulifera extract did not show cytotoxicity in macrophages, and inflammatory cytokines IL-1β and IL induced by LPS, an endotoxin -6, it was found that it exhibits anti-inflammatory activity that significantly inhibits the production of TNF-α.

In addition, as a result of evaluation of anti-atopic activity using HaCaT cells, human keratinocytes, Uncarina stelulifera extract did not show cytotoxicity in the concentration range of 0.16 to 100 μg/mL, and 100 μg/mL At concentration, it was confirmed that the anti-atopic activity significantly inhibited the production of thymus activation-related chemokine (TARC; CCL17), a chemokine involved in atopic production.

The Uncarina stelulifera extract according to the present invention may be extracted and separated from nature using a method known in the art for extraction and separation, and a suitable solvent for extracting the extract from the Uncarina stelulifera As for the furnace, any organic solvent that is pharmaceutically acceptable may be used, and water or an organic solvent may be used, but is not limited thereto, but, for example, purified water, methanol, ethanol, propanol ( propanol), isopropanol, alcohol having 1 to 4 carbon atoms including butanol, acetone, ether, benzene, chloroform, ethyl acetate, Various solvents such as methylene chloride, hexane, and cyclohexane may be used alone or in combination. Preferably, ethanol (alcohol) may be used, and more preferably, 70% ethanol may be used.

As the extraction method, any one of methods such as hot water extraction, cold precipitation extraction, reflux cooling extraction, solvent extraction, steam distillation method, ultrasonic extraction method, elution method, and compression method may be used. In addition, the desired extract may be further subjected to a conventional fractionation process, or may be purified using a conventional purification method. There is no limitation on the method for preparing the Uncarina stelulifera extract of the present invention, and any known method may be used.

Accordingly, in the present invention, the Uncarina stelulifera extract is a concept including all extracts, fractions and purified products obtained in each step of extraction, fractionation, or purification, and their dilutions, concentrates, or dried products.

In addition, the present invention provides an anti-inflammatory or anti-atopic cosmetic composition comprising the extract of Uncarina stelulipera as an active ingredient.

In one embodiment of the present invention, the Uncarina stelulifera extract or a fraction thereof may be included in the cosmetic composition at a concentration of 1 μg/ml to 1000 μg/ml (or 1 to 1000 ppm).

Products to which the cosmetic composition of the present invention can be added include, for example, astringent lotion, softening lotion, nutrient lotion, various creams, essences, packs, and cosmetics such as foundation, and cleansing, face wash, soap, treatment, beauty liquid Etc.

Specific formulations of the cosmetic composition of the present invention include flexible lotions, gels, water-soluble liquids, milk lotions, nutrition creams, massage creams, essences, oil-in-water emulsions, water-in-oil emulsions, anhydrous face products, solid anhydrous products, and globules. Oil dispersion in used aqueous phase, ionic lipid vesicle, nonionic lipid vesicle, ointment, cleansing foam, cleansing water, pack, body oil, oil-in-water makeup base, water-in-oil makeup base, foundation, skin cover, lipstick, It includes one formulation selected from the group consisting of lip gloss, face powder, two-way cake, eye shadow, mascara, cheek color, and eyebrow pencil.

According to a preferred embodiment of the present invention, the content of the active ingredient (Uncarina stelulifera extract or a fraction thereof) of the present invention is 0.01-40% by weight based on the total weight of the composition, and if it is less than 0.1% by weight, inflammation or atopy improvement and The treatment effect is greatly reduced, and if it exceeds 40% by weight, the original quality of the product may not be realized or cost efficiency may decrease.

The cosmetic composition of the present invention may be used alone or in duplicate, or may be used in duplicate with other cosmetic compositions other than the present invention. In addition, the cosmetic composition having an excellent effect on inflammation and atopic diseases according to the present invention may be used according to a conventional method of use, and the number of times of use thereof may be varied according to a user's skin condition or taste.

In addition, the present invention provides an anti-inflammatory or anti-atopic pharmaceutical composition comprising an extract of Uncarina stelulifera as an active ingredient.

The route of administration of the pharmaceutical composition according to the present invention includes oral, intravenous, intramuscular, intraarterial, transdermal, subcutaneous, intraperitoneal, intranasal, intestinal, topical, sublingual or rectal, parenteral administration is preferred, More preferably, it is applied in a method of topical application by application. The parenteral includes subcutaneous, intradermal, intravenous, intramuscular, intralesional injection or infusion techniques.

The pharmaceutical composition of the present invention may contain one or more active ingredients exhibiting the same or similar functions in addition to the Uncarina stelulifera extract of the present invention. Each of the above compositions may be formulated and used in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, etc., external preparations, suppositories, and sterile injectable solutions according to a conventional method.

Solid preparations for oral administration include powders, granules, tablets, capsules, soft capsules, and pills. Liquid preparations for oral use include suspensions, liquid solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweetening agents, fragrances, and preservatives may be included. . Formulations for parenteral administration include powders, granules, tablets, capsules, sterilized aqueous solutions, solutions, non-aqueous solutions, suspensions, emulsions, syrups, suppositories, aerosols, and other external and sterile injection formulations, respectively, according to conventional methods. Formulated in a form and used, preferably, a pharmaceutical composition for skin external use of cream, gel, patch, spray, ointment, warning agent, lotion, liniment, pasta, or cataplasma may be prepared and used. , But is not limited thereto. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate may be used. As a base for suppositories, witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin, and the like may be used.

The composition may further contain an adjuvant such as a preservative, a stabilizer, a hydrating agent or an emulsification accelerator, a salt and/or a buffer for controlling the osmotic pressure, and other therapeutically useful substances, and a conventional method of mixing, granulating or It can be formulated according to the coating method.

The pharmaceutical composition of the present invention may vary according to various factors including age, weight, general health, sex, administration time, route of administration, excretion rate, drug formulation, and severity of a specific disease of the individual.

A suitable dosage of the pharmaceutical composition of the present invention is formulated in various ways depending on factors such as formulation method, mode of administration, age, weight, sex, pathological condition, food, administration time, route of administration, excretion rate and response sensitivity. Can be. The dosage of the pharmaceutical composition of the present invention is in the range of 0.001 to 100 mg/kg on an adult basis. In addition, in the case of an external preparation, it is recommended to apply once to 5 times a day in an amount of 10 to 30 ml on an adult basis and continue for more than 1 month, but the dosage is not intended to limit the scope of the present invention.

In addition, the present invention provides a health food composition for preventing or improving inflammation and atopy, comprising an extract of Uncarina stelulifera as an active ingredient.

The health food of the present invention may be used in combination with other foods or food ingredients, or may be appropriately used according to a conventional method by adding a composition containing the extract of Uncarina stelusfera as an active ingredient.

There is no particular limitation on the kind of the health food. Examples of foods to which a composition containing the Uncarina stelulifera extract as an active ingredient can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, ice cream, etc. There are dairy products, various soups, beverages, teas, drinks, alcoholic beverages and vitamin complexes, and all health foods in the usual sense are included.

When the composition of the present invention is prepared as a health food composition, it may include ingredients that are commonly added during food production, and include, for example, proteins, carbohydrates, fats, nutrients, flavoring agents and flavoring agents. Examples of the carbohydrate include monosaccharides such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose, oligosaccharides, and the like; And polysaccharides, for example, common sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As the flavoring agent, a natural flavoring agent taumatin, a stevia extract, and a synthetic flavoring agent may be used. For example, when the health food composition of the present invention is prepared as a drink, citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, fruit juice, natural extracts, etc. may be additionally included in addition to the Uncarina stelulifera extract of the present invention.

In addition, the present invention provides an anti-inflammatory or anti-atopy quasi-drug composition comprising an extract of Uncarina stelulifera as an active ingredient.

The quasi-drug composition of the present invention may further include a pharmaceutically acceptable carrier, excipient, or diluent as needed in addition to the above ingredients. The pharmaceutically acceptable carrier, excipient, or diluent is not limited as long as it does not impair the effects of the present invention, for example, fillers, extenders, binders, wetting agents, disintegrants, surfactants, lubricants, sweeteners, fragrances, preservatives, etc. Can include.

The quasi-drug composition of the present invention may exemplify a disinfectant cleaner, a shower foam, an ointment, a wet tissue, a coating agent, etc., but is not limited thereto, and the formulation method, dosage, usage method, component, etc. of quasi-drugs are known in the art. It can be appropriately selected from the techniques of.

In addition, the Uncarina stelulifera extract of the present invention can be used for anti-inflammatory or anti-atopic, including the step of applying to the skin of an individual. The subject includes, without limitation, mammals including mice, livestock, humans, and the like.

Hereinafter, the present invention will be described in more detail through examples. These examples are for explaining the present invention more specifically, and the scope of the present invention is not limited to these examples.

< Example 1> Uncarina Stellurifera Method for producing extract

20 times of 70% ethanol was added to Uncarina stelulifera outpost (50 g), extracted at 80° C. for 3 hours, cooled and filtered. Separated and concentrated for 20 minutes at 8000 rpm using a centrifuge, and then lyophilized. The dried Uncarina stelulifera 70% ethanol extract was dissolved in DMSO (dimethyl sulfoxide) at a high concentration of 100 mg/mL, and then diluted stepwise in deionized water and readjusted to a concentration of 0.1 mg/mL (the final concentration of DMSO Is 0.1%), this was for the present inventors to adjust the concentration conditions of DMSO does not appear to be toxic to the cells.

< Example 2> Uncarina Stellurifera Evaluation of anti-inflammatory activity of extract

To evaluate the anti-inflammatory effect of Uncarina stelulifera extract, inhibiting cytotoxic and inflammatory cytokines (IL-1β, IL-6, TNF-α) and nitric oxide (NO) in RAW 264.7 inflamed with lipopolysaccharide (LPS). The activity was measured.

Specifically, to evaluate the cytotoxicity of Uncarina stelulifera extract, RAW 264.7 cells were plated on a 96 well plate at 1×10 ⁶ cells/mL and cultured in a 37°C, 5% CO ₂ incubator for 24 hours to stabilize the cells. Made it. Thereafter, all the culture medium of the cells was removed, 160 μL of DMEM medium containing 0.2% FBS and 1% P/S and 20 μL of an appropriately diluted sample were added, and after 30 minutes LPS (1 μg/mL) as an inflammatory substance. After addition, it was rearranged for 24 hours. The toxicity of RAW 264.7 cells by the sample was measured using the above-mentioned MTT solution to adherent cells from which all of the culture supernatant was removed, and expressed as cell viability (%) for the sample untreated group.

As a result, the Uncarina stelulifera extract showed a cell viability of 100% or more compared to the untreated group (negative control group) in a concentration range of 200 μg/mL or less, showing no cytotoxicity (FIG. 2 ).

In addition, cytokines are proteins secreted by immune cells and are factors that mediate the inflammatory response by regulating the activity, proliferation and differentiation of immune cells. The role of cytokine is very important to investigate the cause and treatment of inflammatory diseases, and TNF-α, IL-1β, and IL-6 are known as representative inflammatory cytokines as substances that regulate inflammatory responses both in vitro and in vivo. have.

Tumor necrosis factor-alpha, an inflammatory cytokine released as a cell culture supernatant, to determine how Uncarina stelulifera extract affects the inhibitory activity of IL-1β, IL-6, and TNF-α production increased on LPS. TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) contents were measured by sandwich ELISA, respectively, and nitric oxide (NO) contents were measured by Griess method. The content of TNF-α, IL-1β, and IL-6 analyzed by ELISA method is produced by standard curves prepared using lyophilized recombinant TNF-α, IL-1β and IL-6 proteins provided by the manufacturer (pg/mL). ), and the content of NO was quantified in μM through sodium nitrite (NaNO ₂ ).

As a result, Uncarina stelulifera extract concentration-dependently inhibits the production of inflammatory cytokines IL-1β, IL-6 and TNF-α induced by endotoxin LPS, as well as 200 μg of Uncarina stelulifera extract The effect of inhibiting production of IL-1β and IL-6 was excellent at /mL (FIGS. 3 to 5 ).

Specifically, in the results of IL-1β inhibitory activity, when Uncarina stelulifera extract was treated at a concentration of 200 μg/mL, it showed an excellent inhibitory effect of 82.1% compared to the LPS control group, and in the case of IL-6, 8-200 μg/mL In mL, the concentration-dependent increased inhibitory activity (9.5~80.3% inhibition compared to the LPS control group) was shown. In the TNF-α production inhibitory activity, at a concentration of 200 μg/mL, the inhibitory effect was 30.2% compared to that of the LPS control group, and when combined, Uncarina stelulifera extract was judged to have very excellent anti-inflammatory effect of inhibiting inflammatory cytokines. Became.

In addition, in the NO production inhibitory activity result, the LPS control group showed a significant inhibitory activity (10.4 to 15.5% inhibition compared to the LPS control group) in a concentration range of 8 to 200 μg/mL (Fig. 6).

< Example 3> Uncarina Stellurifera Extract of Anti-atopy Activity assay

HaCaT cytotoxicity and TARC inhibitory activity were analyzed to evaluate the anti-atopic activity of Uncarina stelulifera extract.

Specifically, cells were used in DMEM medium (hereinafter referred to as HaCaT-culture medium) to which 10% FBS and 1% P/S were added, and passaged once every 2-3 days in an incubator maintained at 37°C and 5% CO ₂ conditions. It was cultured and used for experiments. HaCaT cells were plated on a 96-well plate at 1×10 ⁵ cells/mL and cultured in a 37°C, 5% CO ₂ incubator to stabilize the cells.After 24 hours, all the supernatant of the medium was removed and 40 μL of PBS was added. It was placed in a UV irradiation device and UVB (312 nm) was irradiated with a light amount of 20 mJ/cm ² . Subsequently, PBS was removed, 180 μL of fresh HaCaT-culture medium and 20 μL of a sample diluted to an appropriate concentration were added, followed by cultivation for 48 hours. The evaluation of cytotoxicity by the sample was measured by the MTT method as mentioned above, and was expressed as cell viability (%) for the sample untreated group (UV-). TGF-β (20 nm/mL) was used as a positive control for the anti-atopic activity comparison with Uncarina stelulifera extract. Only the culture supernatant was recovered and the content of thymus activation-related chemokine (TARC; CCL17), an atopic chemokine released as the supernatant, was measured by ELISA set, and the amount of production (pg/mL) through a standard curve prepared by recombinant TARC protein. Calculated.

As a result, in the concentration range of 0.16-100 μg/mL, Uncarina stelulifera extract exhibited a survival rate of 102.2-104.5%, and it was confirmed that there was no toxicity to cells (FIG. 7).

In addition, Uncarina stelulifera extract inhibited the production of TARC secreted by UV-stimulated HaCaT cells in a concentration-dependent trend. Specifically, it showed 0.7 to 41.0% of TARC production inhibitory activity compared to the UV treatment control (UV+) in the concentration range of 4 to 100 μg/mL, and in particular, a significant inhibitory activity was confirmed at 100 μg/mL. Through this result, it was determined that Uncarina stelulifera extract has excellent anti-atopic activity (FIG. 8).

Claims (10)

delete delete Uncarina stelulifera ( Uncarina stellulifera ) pharmaceutical composition for the prevention or treatment of inflammation or atopic dermatitis comprising an extract as an active ingredient. The composition of claim 3, wherein the extract is prepared by extracting with a solvent selected from the group consisting of water, alcohol having 1 to 4 carbon atoms, and a mixed solvent thereof. Cosmetic composition for the prevention or improvement of inflammation or atopic dermatitis, comprising an extract of Uncarina stellulifera (Uncarina stellulifera) as an active ingredient. The method of claim 5, wherein the cosmetic composition is a flexible lotion, gel, water-soluble liquid, milk lotion, nutrition cream, massage cream, essence, oil-in-water emulsion, water-in-oil emulsion, anhydrous face product, anhydrous solid product, globules Oil dispersion in the aqueous phase, ionic lipid vesicles, nonionic lipid vesicles, ointment, cleansing foam, cleansing water, pack, body oil, oil-in-water makeup base, water-in-oil makeup base, foundation, skin cover, lipstick, lip Gross, face powder, two-way cake, eye shadow, mascara, cheek color and eyebrow pencil, which is one type of formulation selected from the group consisting of, a cosmetic composition. delete Health functional food composition for the prevention or improvement of inflammation or atopic dermatitis, comprising an extract of Uncarina stellulifera (Uncarina stellulifera) as an active ingredient. A quasi-drug composition for preventing or improving inflammation or atopic dermatitis, comprising an extract of Uncarina stellulifera as an active ingredient.
Uncarina stelulifera (Uncarina stellulifera) containing an extract as an active ingredient, a composition for external application for skin for the prevention and treatment of inflammation or atopic dermatitis.

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