KR20240019711A - Composition for Improving Skin Microbiota Comprising Umbelliferone or Derivatives Thereof - Google Patents

Abstract

The present invention relates to a composition for improving skin microbial flora containing umbelliferone or a derivative thereof.
The composition according to the present invention, including umbelliferone or a derivative thereof, can exhibit the effect of improving the skin microbial flora by promoting the growth of microorganisms beneficial to the skin and inhibiting the growth of microorganisms harmful to the skin. Accordingly, the composition for improving skin microbial flora of the present invention can be effectively used in cosmetic compositions for improving skin and pharmaceutical compositions for preventing or treating skin diseases.

Description

Composition for Improving Skin Microbiota Comprising Umbelliferone or Derivatives Thereof}

The present invention relates to a composition for improving skin microbial flora containing umbelliferone or a derivative thereof, and more specifically, to a composition containing umbelliferone or a derivative thereof for improving the growth of beneficial skin bacteria while suppressing the growth of harmful skin bacteria. It relates to a composition that can improve microbial flora.

The skin is a tissue of the integumentary system that plays a central role in innate immunity that protects the human body. It exists on the outside and is constantly exposed to harmful substances such as pathogenic microorganisms and fine dust. Even healthy skin develops infection symptoms when exposed to highly pathogenic microorganisms, and the help of symbiotic microorganisms on the skin is needed to suppress this.

In the skin microbiome, the microbial flora that exists on the skin, beneficial and harmful bacteria coexist. For example, Staphylococcus aureus , which exists on the skin, is one of the causative bacteria that causes skin diseases, and is a harmful bacteria that is abnormally distributed in areas with atopic dermatitis or causes purulent skin inflammation. Therefore, in order to prevent or treat skin diseases, substances with antibacterial and growth inhibitory effects on harmful bacteria such as Staphylococcus aureus have been studied.

For example, in Republic of Korea Patent Publication No. 10-2313769, Lactobacillus plantarum strains derived from pickled foods have antibacterial and growth inhibition properties against Staphylococcus aureus (Staphylococcus aureus) and Propionibacterium acnes. It is stated that it can be effective.

However, when using live microorganisms in this way, there is a disadvantage that stability during distribution and storage is not high. In addition, beneficial effects appear when a balanced microbial flora of harmful and beneficial bacteria is formed on the skin, but the above technology only describes the effect on skin harmful bacteria and does not consider technical measures to promote beneficial skin bacteria.

Meanwhile, Staphylococcus epidermidis is one of the most common bacteria on the skin, and according to the literature [Baviera et al., BioMed Research International , 2014, 436921], it is a beneficial bacteria in the skin microbial flora and produces antibacterial peptides against pathogens. It has been reported to produce, maintain skin barrier function, and influence immune responses.

In this way, symbiotic bacteria that are beneficial to the skin secrete substances that inhibit the growth of microorganisms or make the skin slightly acidic, inhibiting the growth of other microorganisms, and stimulating the body's immune system to enhance response to pathogenic microorganisms and invade the skin. This reduces skin contact with pathogenic microorganisms. Therefore, in order to maintain healthy skin, you must receive help from symbiotic bacteria that are beneficial to the skin, and when the balance between microorganisms in the flora is broken, skin diseases develop.

Accordingly, in order to improve the skin microbial flora, research is needed on substances that can selectively promote the growth of beneficial bacteria while suppressing the growth of harmful skin bacteria, rather than substances that simply kill or inhibit the growth of harmful bacteria.

The purpose of the present invention is to provide a composition that improves skin microbial flora by selectively controlling the growth of skin microorganisms.

Another object of the present invention is to provide a cosmetic composition for improving skin comprising the composition for improving skin microbial flora.

Another object of the present invention is to provide a pharmaceutical composition for preventing or treating skin diseases, including the composition for improving skin microbial flora.

In order to achieve the above-described object, the present invention provides a composition for improving skin microbial flora containing umbelliferone or a derivative thereof.

In the present invention, the concentration of the umbelliferone or its derivative may be 0.1 to 20mM.

In the present invention, the composition for improving skin microbial flora can promote the growth of beneficial skin bacteria and inhibit the growth of harmful skin bacteria.

In the present invention, the beneficial skin bacteria may be Staphylococcus epidermidis .

In the present invention, the skin harmful bacteria may be Staphylococcus aureus .

The present invention also provides a cosmetic composition for improving skin, including the composition for improving skin microbial flora.

The cosmetic composition of the present invention may be used to improve atopic skin or acne skin.

The present invention also provides a pharmaceutical composition for preventing or treating skin diseases, comprising the composition for improving skin microbial flora.

In the present invention, the skin disease may be selected from the group consisting of atopic dermatitis, acne, contact dermatitis, and seborrheic dermatitis.

The composition for improving skin microbial flora according to the present invention contains umbelliferone or a derivative thereof and has the activity of promoting the growth of microorganisms beneficial to the skin and inhibiting the growth of pathogenic microorganisms harmful to the skin. Accordingly, the composition for improving skin microbial flora of the present invention exhibits skin prebiotic activity that selectively regulates the growth of skin microorganisms, and can improve the skin microbial flora. Therefore, the composition for improving skin microbial flora of the present invention can be effectively used in cosmetic compositions for improving skin and pharmaceutical compositions for preventing or treating skin diseases.

Figure 1 shows the growth curves of Staphylococcus epidermidis (a) and Staphylococcus aureus (b) as a result of treatment with umbelliferon according to an embodiment of the present invention.
Figure 2 shows the change in doubling time of Staphylococcus epidermidis and Staphylococcus aureus by treatment with umbelliferone in one embodiment of the present invention.
Figure 3 shows changes in cell density of Staphylococcus epidermidis (a) and Staphylococcus aureus (b) due to umbelliferon when Staphylococcus epidermidis and Staphylococcus aureus were mixed cultured in an embodiment of the present invention.

Hereinafter, specific implementation forms of the present invention will be described in more detail. Unless otherwise defined, all technical and scientific terms used in this specification have the same meaning as commonly understood by a person skilled in the art to which the present invention pertains. In general, the nomenclature used herein is well known and commonly used in the art.

The present invention relates to a composition for improving skin microbial flora containing umbelliferone or a derivative thereof.

In this specification, “microbiota” refers to a microbial community including bacteria, fungi, and other prokaryotes present in the human body, and “skin microbiota” refers to the microbial community present on the skin. It means microbial flora. The skin microbial flora includes skin harmful bacteria that cause harmful skin symptoms such as dermatitis, acne, and suppuration, and skin beneficial bacteria that have beneficial effects on the skin, such as maintaining skin moisture, removing active oxygen, and inhibiting the growth of harmful bacteria.

In this specification, “improvement of skin microbial flora” refers to a state in which the skin microbial flora changes in a direction beneficial to the human body. Specifically, it refers to the activity of suppressing the growth of harmful bacteria on the skin and promoting the growth of beneficial bacteria. can do.

The present invention is characterized by improving the skin microbial flora by suppressing the growth of harmful skin bacteria and promoting the growth of beneficial bacteria by using umbelliferone or a derivative thereof. Umbelliferone, used as an active ingredient in the present invention, is represented by the following formula (1).

[Formula 1]

In explaining the present invention, a derivative of umbelliferone may mean that a portion of the oxygen or hydrogen contained in umbelliferone is replaced with another element or substituent. At this time, the substituent is hydrogen; Substituted or unsubstituted alkyl group, alkenyl group, alkynyl group, alkoxy group, ester group, carbonyl group, amine group or heteroalkyl group having 1 to 6 carbon atoms; hydroxyl group; thiol group; amino group; Cyano group; Carboxyl group; aldehyde group; phosphate group; diphosphate group; It may be one or more functional groups selected from the group consisting of a sulfonic acid group and a halogen.

In the term “substituted or unsubstituted” as used herein, “substitution” means replacing a hydrogen atom in a functional group with another functional group (substituent). For example, “substitution” means that one or more of the hydrogen atoms of a functional group are replaced by one or more of the above substituents, i.e., hydrogen; Substituted or unsubstituted alkyl group, alkenyl group, alkynyl group, alkoxy group, ester group, carbonyl group, amine group or heteroalkyl group having 1 to 6 carbon atoms; hydroxyl group; thiol group; amino group; Cyano group; Carboxyl group; aldehyde group; phosphate group; diphosphate group; It may be replaced with one or more functional groups selected from the group consisting of sulfonic acid groups and halogens.

The term “alkyl group” refers to a hydrocarbon group linked by a single bond, and may be, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, etc. The terms “alkenyl group” and “alkynyl group” may have one or more double bonds or triple bonds in a hydrocarbon group. For example, alkenyl groups include vinyl, 2-propenyl, 2-propenyl, and 2-propenyl. -It may be isopentenyl, etc., and the alkynyl group may be ethynyl, propynyl, 3-butynyl, etc. In the present invention, hydrocarbon groups can be interpreted to encompass straight-chain and branched-chain types.

In the present invention, the term "alkoxy group" may be a functional group in which a hydrocarbon group is connected to oxygen, for example -OCH ₃ , -OCH ₂ CH _3, etc., and the term "ester group" may refer to an ester. It may be a functional group that forms a bond, for example -C(=O)-O-CH ₃ , -C(=O)-O-CH ₂ CH ₃ , etc., and the term "carbonyl group" refers to a ketone It may be a functional group that forms a bond, for example -C(=O)-CH ₃ , -C(=O)-CH ₂ CH ₃ , etc., and the term "amine group" refers to a hydrocarbon group connected to nitrogen. It may be a functional group, for example -NHCH ₃ , -N(CH ₃ ) ₂ , etc. In addition, the term "heteroalkyl group" refers to a hydrocarbon group having a structure in which at least one heteroatom selected from the group consisting of oxygen (O), nitrogen (N), and sulfur (S) is connected to two or more carbons. It may be a functional group, for example -CH ₂ -CH ₂ -O-CH ₃ , -CH ₂ -CH ₂ -NH-CH ₃ , -CH ₂ -CH ₂ -N(CH ₃ )-CH ₃ , etc.

The active ingredient of the present invention may be used in hydrate form. Hydrate is a substance containing water molecules within the molecule and is in the form of a compound nH ₂ O, and n may range from 1 to 10.

The composition for improving skin microbial flora containing umbelliferone or a derivative thereof of the present invention as an active ingredient selectively inhibits the growth of harmful bacteria while activating the growth of beneficial bacteria, thereby removing all microorganisms without distinguishing between beneficial and harmful bacteria. Problems with technology can be solved. In particular, it has a special advantage in that it can selectively promote or inhibit growth depending on the species, even though it is a strain that belongs to the same genus taxonomically.

In the present invention, the expression “including as an active ingredient” means including an amount sufficient to achieve the efficacy or activity of umbelliferone or a derivative thereof. In the composition of the present invention, the concentration of umbelliferone or its derivative may be 0.1 to 20mM, specifically 0.5 to 10mM. In the above concentration range, it is preferable because the selective control activity of the growth of beneficial and harmful bacteria on the skin can be more effectively displayed.

Specifically, umbelliferone or a derivative thereof contained in the composition for improving skin microbial flora of the present invention can inhibit the growth of Staphylococcus aureus , a skin-harmful bacteria, and Staphylococcus epidermidis , a skin-beneficial bacteria. can promote the growth of

Staphylococcus aureus is a gram-positive anaerobic bacterium that exists on the skin and nasal surfaces of humans and livestock, and is known to be the causative agent of purulent diseases such as skin purulence, otitis media, and cystitis. In addition, it has been reported that 80-90% of atopic patients have a very high proportion of Staphylococcus aureus on their skin, and that controlling the growth of Staphylococcus aureus is related to dermatological diseases, such as atopic dermatitis.

Meanwhile, Staphylococcus epidermidis is a common bacteria that is not harmful to the human body, has an anti-inflammatory effect, and can play a role in normalizing the microbial flora by suppressing the overgrowth of harmful skin bacteria such as Staphylococcus aureus. It is a beneficial bacteria that is involved in improving the skin, such as normalizing pH and skin barrier against external harmful factors.

As such, the composition for improving the skin microbial flora of the present invention exhibits the effect of improving the skin microbial flora by inhibiting the growth of the skin harmful bacteria and promoting the growth of the skin beneficial bacteria. Accordingly, the composition of the present invention can have skin-improving effects, such as adjusting skin pH and strengthening the barrier, improving acne, atopic dermatitis, and other inflammatory skin, or preventing or treating such skin diseases.

Accordingly, the present invention can also provide a cosmetic composition containing the composition for improving skin microbial flora.

The cosmetic composition of the present invention contains umbelliferone or a derivative thereof as an active ingredient and can improve the microbial flora of the skin, so it can be used as a functional cosmetic to improve skin conditions such as strengthening the skin barrier, adjusting pH, and moisturizing. , In particular, it can be used to improve problematic skin such as atopic skin and acne skin.

In the present invention, the formulation of the cosmetic composition can be prepared in any formulation commonly prepared in the art, for example, solution, emulsion, suspension, paste, gel, cream, lotion, powder, soap, cleansing , may be a formulation selected from the group consisting of oil, powder, or spray.

In the present invention, when the formulation of the cosmetic composition is a solution or emulsion, a solvent, solvating agent, or emulsifying agent can be used as a carrier component. For example, water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol, or fatty acid ester of sorbitan can be used.

In the present invention, when the formulation of the cosmetic composition is a suspension, the carrier component includes water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, and polyoxyethylene sorbitan ester, Microcrystalline cellulose, aluminum metahydroxide, bentonite, agar, or tracant may be used.

In the present invention, when the formulation of the cosmetic composition is a paste, gel, cream or lotion, animal fiber, plant fiber, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or Zinc oxide, etc. may be used.

In the present invention, when the formulation of the cosmetic composition is powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, or polyamide powder can be used as the carrier ingredient, and especially in the case of spray, chlorofluorohydride may be used as a carrier ingredient. May contain propellants such as carbon, propane/butane or dimethyl ether.

In the present invention, when the formulation of the cosmetic composition is cleansing, the carrier ingredients include aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyl taurate, sarcosinate, and fatty acid amide. Ether sulfate, alkylamidobetaine, fatty alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, linoline derivative, or ethoxylated glycerol fatty acid ester can be used.

The cosmetic formulation of the present invention also includes other ingredients that can have a synergistic effect on the main effect within a range that does not impair the main effect aimed at by the present invention, without difficulty depending on the formulation or purpose of use of the cosmetic. You can select and mix them.

In the present invention, the use and function of the cosmetic composition are not particularly limited and can be appropriately selected depending on the purpose. For example, the cosmetic composition of the present invention includes skin lotion, skin softener, skin toner, astringent, lotion, milk lotion, moisture lotion, nutritional lotion, massage cream, nutritional cream, moisture cream, hand cream, foundation, essence, nutritional essence. , pack, soap, cleansing foam, cleansing lotion, cleansing cream, body lotion, and body cleanser may have one or more uses and functions selected from the group.

The cosmetic composition of the present invention may contain not only umbelliferone or its derivatives, but also ingredients commonly used in cosmetic compositions, such as antioxidants, stabilizers, moisturizers, solubilizers, vitamins, ultraviolet absorbers, pigments and fragrances. It may contain common auxiliaries such as preservatives, disinfectants, etc.

The present invention can also provide a pharmaceutical composition for preventing or treating skin diseases, including the composition for improving skin microbial flora.

The pharmaceutical composition contains umbelliferone or a derivative thereof as an active ingredient, and exerts an effect of improving the skin microbial flora by suppressing the growth of harmful skin bacteria and promoting the growth of beneficial skin bacteria. Therefore, the pharmaceutical composition of the present invention can be used for the prevention or treatment of inflammatory skin diseases such as atopic dermatitis, acne, contact dermatitis, and seborrheic dermatitis.

In addition to umbelliferone or a derivative thereof, the pharmaceutical composition may further include an appropriate pharmaceutically acceptable carrier, excipient, or diluent according to a conventional method. The pharmaceutically acceptable carriers are those commonly used in preparation, and include lactose, dextrose, sucrose, sorbitol, mannitol, starch, gum acacia, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, Includes, but is not limited to, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil.

In addition to the above components, the pharmaceutical composition of the present invention may further include lubricants, wetting agents, sweeteners, flavoring agents, emulsifiers, suspending agents, preservatives, etc. Regarding suitable pharmaceutically acceptable carriers and formulations, they can be preferably formulated according to each ingredient using the method disclosed in Remington's Pharmaceutical Sciences (19th ed., 1995).

The pharmaceutical composition of the present invention can be administered either orally or parenterally, and parenteral administration includes transdermal administration, intravenous injection, subcutaneous injection, intramuscular injection, and intraperitoneal injection. Preferably, the pharmaceutical composition of the present invention can be used as an external agent and administered transdermally.

Dosage forms for oral administration include, for example, tablets, pills, hard and soft capsules, solutions, suspensions, emulsifiers, syrups, granules, etc. These dosage forms contain diluents (e.g. lactose, dextrose, water) in addition to the active ingredient. crose, mannitol, sorbitol, cellulose and/or glycine), lubricants (e.g. silica, talc, stearic acid and magnesium or calcium salts thereof and/or polyethylene glycol). Additionally, the tablets may contain binders such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and/or polyvinylpyrrolidine, and in some cases starch, agar, alginic acid. or disintegrants such as sodium salts thereof or effervescent mixtures and/or absorbents, colorants, flavoring and sweetening agents. The formulation can be prepared by conventional mixing, granulating or coating methods.

In addition, representative formulations for parenteral administration are injectable formulations, and solvents for the injectable formulation include water, Ringer's solution, isotonic saline solution, or suspension. The sterile fixed oil of the injectable preparation can be used as a solvent or suspending medium, and any non-irritating fixed oil, including mono- and di-glycerides, can be used for this purpose. Additionally, the injectable preparation may use fatty acids such as oleic acid.

The composition according to the present invention is administered in a pharmaceutically effective amount. In the present invention, "pharmaceutically effective amount" means an amount sufficient to treat a disease with a reasonable benefit/risk ratio applicable to medical treatment, and the effective dose level is determined by the type, severity, and activity of the patient's disease. , can be determined based on factors including sensitivity to the drug, time of administration, route of administration and excretion rate, duration of treatment, drugs used simultaneously, and other factors well known in the field of medicine. The composition according to the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered singly or multiple times. Considering all of the above factors, it is important to administer an amount that can achieve the maximum effect with the minimum amount without side effects, and this can be easily determined by a technician with ordinary knowledge.

Specifically, the effective amount of the composition according to the present invention may vary depending on the patient's age, gender, and weight, and is generally administered at 0.001 to 500 mg per 1 kg of body weight, preferably 0.01 to 100 mg every day or every other day, or 1 to 1 mg per day. It can be administered in three divided doses. However, since it may increase or decrease depending on the route of administration, gender, weight, age, etc., the above dosage does not limit the scope of the present invention in any way.

Example

The present invention will be described in more detail through examples below. However, these examples show some experimental methods and configurations to illustratively illustrate the present invention, and the scope of the present invention is not limited to these examples.

Experiment preparation: strain pre-culture

Staphylococcus epidermidis ( S. epidermidis KCTC 1917) was used as a skin-beneficial bacteria, and Staphylococcus aureus ( S. aureus KCTC 3881) was used as a skin-harmful bacteria.

Each bacteria was plated in three layers on solid medium (Nutrient agar) and cultured at 37°C for 24 hours. Afterwards, a single colony was taken, placed in 20mL Nutrient broth, grown by culturing at 37°C, 250rpm, 18 hours, and used in the experiment.

Experimental Example 1: Analysis of differences in growth rates of beneficial and harmful skin bacteria by treatment with umbelliferon

20 mL of nutrient broth was treated with 2mM of umbelliferone, and the pre-cultured bacteria were inoculated to a concentration of 0.05 (OD ₆₀₀ ) . As a control, samples not containing umbelliferon were inoculated with bacteria in the same manner. Afterwards, main culture was performed (37°C, 250 rpm) for 6 hours, and absorbance was measured at a wavelength of 600 nm every hour. A growth curve of bacteria over time was prepared on a log scale using the recorded absorbance values, and the growth curves of S. epidermidis (a) and S. aureus (b) are shown in Figure 1.

In addition, the results of calculating the doubling time by determining the straight line of the exponential phase are shown in FIG. 2 and Table 1 below. Doubling time refers to the time it takes for the number of cells to double when a microorganism grows exponentially.

division Control Umbelliferon S. epidermidis 100.68 60.19 S. aureus 50.62 68.89

According to the above experimental results, when treated with umbelliferon, the growth rate of S. epidermidis was faster and the doubling time was shorter than that of the control group, while the growth rate of S. aureus was slow and the doubling time was longer.

Through this, it was confirmed that umbelliferone can promote the growth of S. epidermidis, a skin beneficial bacteria, and inhibit the growth of S. aureus , a harmful skin bacteria.

Experimental Example 2: Measurement of changes in cell density of beneficial and harmful skin bacteria by treatment with umbelliferon

20 mL of nutrient broth was treated with 2mM of umbelliferone, and pre-cultured S. epidermidis and S. aureus were each inoculated together to a concentration of 0.05 (OD ₆₀₀ ). As a control, samples not containing the above substances were inoculated with bacteria in the same manner.

Afterwards, main culture was performed (37°C, 250rpm) for 3 hours and diluted to an appropriate concentration using Nutrient broth. 100 μL of the diluted culture was spread on a nutrient agar plate, cultured at 37°C for 24 hours, and cell density (colony forming unit/mL, CFU/mL) was measured.

Using each cell density value obtained from the above experiment, relative cell growth change (%) was calculated according to the formula below.

S. epidermidis (a) with or without umbelliferon treatment and S. aureus (b) are shown in Figure 3, and the relative cell growth changes of each bacteria calculated from this are shown in Table 2 below.

Relative cell growth changes S. epidermidis S. aureus Umbelliferon 3.43 -50.92

Referring to Figure 3 and Table 2, when the two bacteria were cultured together, the experimental group treated with umbelliferone had a slightly higher cell density of S. epidermidis than the control group, while the cell density of S. aureus was very low.

Accordingly, when treating umbelliferon in an environment where beneficial and harmful skin bacteria coexist, the growth of beneficial bacteria was promoted while the growth of harmful bacteria was suppressed, resulting in an improvement in the skin microbial flora.

From the above description, those skilled in the art to which the present invention pertains will understand that the present invention can be implemented in other specific forms without changing its technical idea or essential features. In this regard, the embodiments described above should be understood in all respects as illustrative and not restrictive. The scope of the present invention should be construed as including the meaning and scope of the patent claims described below rather than the detailed description above, and all changes or modified forms derived from the equivalent concept thereof are included in the scope of the present invention.

Claims (9)

A composition for improving skin microbial flora comprising umbelliferone or a derivative thereof as an active ingredient.
According to claim 1,
A composition for improving skin microbial flora, wherein the concentration of umbelliferone or a derivative thereof is 0.1 to 20mM.
According to claim 1,
A composition for improving skin microbial flora, wherein the composition promotes the growth of skin beneficial bacteria and inhibits the growth of skin harmful bacteria.
According to claim 3,
A composition for improving skin microbial flora, wherein the beneficial skin bacteria are Staphylococcus epidermidis .
According to claim 3,
A composition for improving skin microbial flora, wherein the skin harmful bacteria are Staphylococcus aureus .
A cosmetic composition for improving skin, comprising the composition of any one of claims 1 to 5.
According to claim 6,
A cosmetic composition for improving atopic skin or acne skin.
A pharmaceutical composition for preventing or treating skin diseases, comprising the composition of any one of claims 1 to 5.
According to claim 8,
A pharmaceutical composition, wherein the skin disease is selected from the group consisting of atopic dermatitis, acne, contact dermatitis, and seborrheic dermatitis.