TW201703786A - Use of extract of mangosteen rind for treating dermatological diseases - Google Patents

Abstract

The present invention provides a use of a composition for manufacturing medicaments for treating dermatological diseases, wherein the composition comprising an effective amount of mangosteen rind extract.

Description

Mangosteen fruit husk extract for the treatment of skin diseases

The present invention relates to the use of a composition for the manufacture of a medicament for the treatment of skin disorders.

The skin is the largest organ in the human body. The skin diseases are also numerous. The skin diseases may be acute (lasting only a few minutes to several hours) or chronic conditions, which may affect individuals for days, months, years or even a lifetime. Skin diseases may be It is a fungal, bacterial, or viral condition, or may be a non-infectious, immune response, such as an inflammatory response with or without an allergen, or may be an idiopathic disease. Thus, the symptoms may be varied and may range from mild itching, redness and swelling to severe long pus and open pain, such as noxious ulceration, which may materially affect the quality of life of the individual.

Skin diseases may be scarring, dermatitis, proliferative diseases or conditions, mast cell diseases or conditions, burns, contact with allergens and/or irritants, or inflammatory diseases or conditions, skin diseases including atopic dermatitis, large Apes skin disease, collagen disease, psoriasis, psoriasis, contact dermatitis, eczema, urticaria, erythema, hypertrophic scar, tumor Adult, scleroderma, folliculitis, burns or hyperlipidemia of the skin.

Atopic dermatitis, also known as atopic eczema, is an allergic skin disease that is often associated with heredity. It is one of the most common skin diseases in infants and young children, accounting for 3 to 5% of the population of children. 60% of patients will develop symptoms within one year of age, and 30% of patients will develop between 1 and 5 years of age. About half of children with atopic dermatitis will have allergic rhinitis, asthma, allergic conjunctivitis, etc., which are called allergic children, or called atopic physique.

Psoriasis is a common chronic skin disease, also known as psoriasis. It is characterized by the appearance of papules of varying sizes, erythema, covered with silvery white scales, clear boundaries, and occurs in the scalp, the extremities and the back.

Folliculitis is a purulent inflammation that occurs when a bacterium invades the hair follicle. It occurs mostly in the head, neck, buttocks, genitals, perianal or other parts of the body, and is more likely to recur.

Contact dermatitis is an inflammatory reaction of skin mucous membranes due to exposure to foreign substances such as chemical fiber clothing, cosmetics, drugs, and the like. Its clinical features are sharp edges at the contact site, edematous erythema in the light, papules, leeches and even sputum in the heavier, and epidermis loosening or even necrosis in more severe cases.

The general treatment for skin diseases includes oral or topical preparations. Steroids and antihistamines are now widely used in the treatment of allergic diseases of atopic dermatitis, and in severe cases, immunosuppressive agents can be administered. However, these methods only have a short-term therapeutic effect and are prone to adverse side effects such as skin atrophy, skin pigmentation, acne, osteoporosis, avascular necrosis, atherosclerosis, glaucoma, and tumor growth. Wait. Therefore, there is an urgent need to develop a novel therapeutic agent for symptomatic relief and treatment of atopic dermatitis, which provides a powerful and long-lasting therapeutic effect and reduces side effects.

Mangosteen has been researched and applied in the fields of breast cancer prevention and muscle-related diseases, and has also been developed as a nutritional supplement and cosmetics for daily life, as well as for the treatment of acute hepatitis, liver fibrosis and prevention of cirrhosis (Republic of China patent) Bulletin No. I411432).

Matsumoto et al. also studied the purification of α-mangostin, β-mangostin, γ-mangostin, and methyl-β-mangostin from mangosteen husks, and studied the inhibition of this compound on various stages of the cell cycle. The effect shows that the compound has an anti-cell proliferation effect and an anti-tumor effect (Bioorg. Med. Chem. 2005, 13, 6064-6069).

The present invention provides the use of a composition for the preparation of a pharmaceutical composition for the treatment of an immune disorder, an allergic condition or an inflammatory condition.

In particular, the invention provides the use of a composition for the manufacture of a medicament for the treatment of an autoimmune disease or allergy, wherein the composition comprises an effective amount of mangosteen husk extract. The drug can also be used for topical or precise treatment purposes.

The invention further provides the use of a composition for the manufacture of a medicament for the treatment of an autoimmune disease or allergy, wherein the composition comprises an effective amount of mangosteen husk extract.

In a preferred embodiment, the mangosteen husk is extracted by a solvent selected from the group consisting of methanol, ethanol, n-propanol, 2-propanol, n-butanol, acetone, ethyl acetate and A group of water.

In another preferred embodiment, the mangosteen fruit shell extract is mangosteen fruit shell water extract and/or mangosteen fruit shell alcohol extract.

Mangosteen fruit husk refers to the part of the mangosteen fruit that has a softer inner shell and a harder outer shell.

In a preferred embodiment, the mangosteen fruit shell extract is mangosteen fruit shell water extract; in another preferred embodiment, the mangosteen fruit shell shell extract is mangosteen fruit shell alcohol extract.

In a preferred embodiment, the mangosteen husk is a mangosteen shell and/or a mangosteen shell.

In another preferred embodiment, the mangosteen husk is a mangosteen shell.

In a preferred embodiment, the composition further comprises an excipient having a ratio of from 1% to 10%, which is still therapeutically effective.

In a preferred embodiment, the mangosteen husk water extract can relieve itching and/or promote cell proliferation; in another preferred embodiment, the mangosteen husk alcohol extract can be anti-inflammatory and/or analgesic.

In still another preferred embodiment, the mangosteen husk extract inhibits an increase in the immunoregulatory related hormones IL-7 and IL-10, but does not inhibit the inflammatory related cytokine IL-1 or TNF-α. Among them, the mangosteen shell extract mainly inhibited the increase of IL-7 and IL-10, and also inhibited the increase of IL-15 and MCP-1; the extract of mangosteen shell and shell mainly inhibited IL-7, The increase of IL-10 and IL-15 also inhibited the increase of MCP-1.

In a preferred embodiment, the composition further comprises an oil.

In a preferred embodiment, the composition of the present invention may be an oral or parenteral preparation, and the parenteral preparation may be an external preparation, which may be a cream, a cream, an ointment, a gel, or a wash. Agent or patch.

In a preferred embodiment, the mangosteen husk extract of the present invention comprises α-mangostin and γ-mangostin.

In another preferred embodiment, the mangosteen fruit shell water extract of the present invention comprises α-mangostin and γ-mangostin.

In still another preferred embodiment, the mangosteen fruit shell alcohol extract of the present invention comprises α-mangostin and γ-mangostin.

The composition of the present invention can treat or inhibit atopic dermatitis by inhibiting immunomodulatory related hormones, rather than inhibiting inflammatory cytokines such as IL-1 or TNFα.

Skin diseases include, but are not limited to, atopic dermatitis, bullous skin disease, collagen disease, psoriasis, psoriasis, contact dermatitis, eczema, urticaria, erythema, hypertrophic scarring, tumor formation , scleroderma, folliculitis, burns or hyperlipidemia of the skin.

As used herein, the term "allergy disorder" means a disease, condition or condition that is allergic to a generally harmless substance. The materials may be present in the environment (eg, indoor air pollutants and air allergens) or not from the environment (eg, those causing skin or food allergies). Allergens can enter the body via a number of routes, including through breathing, ingestion, skin contact or injection (including insect mites). Many allergic conditions are associated with atopic physique that has a tendency to produce allergic antibodies to IgE. Because IgE can sensitize obese cells anywhere in the body, individuals with atopic physique often show disease in more than one organ. For the purposes of the present invention, an allergic condition includes any allergic reaction that occurs when re-exposed to a sensitizing allergen, which in turn causes release of an inflammatory mediator. Allergic conditions include, but are not limited to, allergic rhinitis (eg, hay fever), sinusitis, rhinosinisitis, chronic or recurrent otitis media, drug reactions, insect spasm, latex response, conjunctivitis, sputum Measles, systemic allergic reactions and allergic reactions, Atopic dermatitis, asthma, and food allergies.

The extract of the present invention can be used for preventing or treating a patient suffering from an inflammatory condition. As used herein, "inflammatory condition" means a disease, condition or symptom characterized by inflammation of the body tissue or an inflammatory component. It includes local inflammatory reactions and systemic inflammation. Examples of such inflammatory conditions include: transplant rejection, including skin graft rejection; chronic inflammatory conditions of the joint including arthritis, rheumatoid arthritis, osteoarthritis, and bone diseases associated with increased bone loss; inflammatory bowel Diseases such as ileitis, ulcerative colitis, Barrett's syndrome and Crohn's disease; inflammatory lung disorders such as asthma, adult respiratory distress syndrome and chronic obstructive respiratory disease; ocular inflammatory conditions, Including corneal dystrophy, trachoma, onchocerciasis, uveitis, sympathetic ophthalmitis and endophthalmitis; chronic gingival inflammatory conditions, including gingivitis and periodontitis; tuberculosis; Insulin; kidney inflammatory diseases, including uremia complications, renal glomerulonephritis and kidney disease; skin inflammatory conditions, including sclerodermatitis, psoriasis and eczema; central nervous system inflammatory diseases, including chronic demyelination of the nervous system Syndrome, multiple sclerosis, AIDS-related neurodegeneration and Alzheimer's disease Infectious meningitis, encephalomyelitis, Parkinson's disease, Huntington's chorea, amyotrophic lateral sclerosis, with viral or autoimmune encephalitis; autoimmune disorders, Immune complex vasculitis, systemic lupus and erythema; systemic lupus erythematosus (SLE); and cardiac inflammatory diseases such as cardiomyopathy, ischemic heart disease (hypercholesterolemia, atherosclerosis); Diseases with significant inflammatory components include pre-eclampsia, chronic liver failure, brain and spinal cord trauma, and cancer. There may also be systemic inflammation such as Gram-positive or Gram-negative shock, hemorrhagic or anaphylactic shock, or shock induced by cancer chemotherapy in response to pro-inflammatory cytokines, such as Shock associated with pro-inflammatory cytokines. This shock can be induced, for example, by a chemotherapeutic agent for cancer chemotherapy. "Treatment of an inflammatory condition" as used herein refers to the administration of a compound or composition of the invention to an individual having an inflammatory condition, a symptom of such condition, or an individual suffering from such disease, in order to treat, slow, alter, affect or prevent the disease. An inflammatory condition, its symptoms, or a predisposition to illness.

An "effective dose" is a dose that achieves an effective result when administered to an individual, or a dose that possesses the desired activity in vivo or in vitro. In the case of an inflammatory condition and an autoimmune condition, effective clinical outcomes include a reduction in the extent or severity of the symptoms associated with the disease or condition, and/or prolonging the life of the individual, and/or improving the quality of life of the individual, as compared to untreated. . The precise amount of compound administered to an individual will depend on the type and severity of the disease or condition, as well as the individual characteristics, such as the general health of the individual, age, sex, weight, and tolerance to the drug. It is also determined by the degree of inflammatory disease, autoimmune disorder, degree of allergy, severity and type, or the immunosuppressive effect sought. Those skilled in the art will be able to determine the appropriate dosage based on these and other factors.

The present invention relates to extracts or pharmaceutical compositions that are particularly useful for immunosuppression, or for treating or preventing inflammation, immune disorders, and allergic conditions.

The pharmaceutical compositions of the present invention can be formulated into a variety of oral or parenteral formulations. The oral preparation can be formulated into a solid preparation such as a powder, granule, lozenge, capsule or the like, or formulated into a liquid preparation such as a suspension, an emulsion, a syrup or the like. The parenteral preparation can be formulated into an external preparation such as a cream, an ointment, a gel, a lotion, a patch, or the like, or a sorbent, an aerosol, a suppository or the like.

The pharmaceutical composition of the present invention may comprise a pharmaceutically acceptable excipient, and in particular may further comprise a predetermined solvent or oil, if desired, and may further comprise a dispersing agent.

Examples of the solvent which can be used in the present invention include, but are not limited to, water, ethanol, isopropanol, 1,3-butylene glycol, propylene glycol, glycerin and the like.

Examples of oils useful in the present invention are selected from the group consisting of corn oil, sesame oil, linseed oil, cottonseed oil, soybean oil, peanut oil, mono-glycerides, di-glycerides, tri-glycerides, mineral oils, deep sea fish. Squalene, jojoba oil, olive oil, evening primrose oil, Borage Oil, grape seed oil, coconut oil, sunflower oil, shea butter, and any combination thereof The group consisting of, but not limited to.

The solvent and the oil may be used singly or in any combination thereof.

Examples of useful dispersing agents may include, but are not limited to, lecithin, organic monoglyceride, sorbitan fatty acid ester, polyoxyethylene fatty acid ester, sorbitan stearate, and the like. These materials may also be used singly or in any combination thereof.

If desired, the composition may further comprise additional ingredients such as antibacterials or preservatives.

Meanwhile, the conventional active ingredient can be used together with the composition as long as it does not have a counteracting effect on the pharmaceutical activity of the composition of the present invention. For example, a moisturizer such as ceramide is commonly used as a conventional atopic dermatitis agent, or a liquid component such as a steroid of hydroxycortisol, a vitamin A derivative such as vitamin A and/or Tocopherols and the like can be used together with the composition.

When a pharmaceutical composition is used as the external preparation, a suitable external skin preparation can be used as a base material, and an aqueous solution, a nonaqueous solvent, a suspension, an emulsion or a lyophilized preparation or the like can be used, which is sterilized by a conventional method.

In the compositions of the invention to be administered or administered, the dosage can vary depending on the Factors such as the route of administration, age, sex, and the weight of the patient, the severity of the disease, and the dosage form as the active ingredient.

Where the composition of the invention may be a food or cosmetic composition, the composition may be prepared by the appropriate addition of at least one food nourishing or cosmetically acceptable carrier.

The food composition can be used or added to, for example, a health food. As used herein, the term "healthy food" means a food product comprising a composition of the invention having an improved function compared to a general food product. Healthy foods can be prepared by adding the composition to a general food product, or by encapsulation, pulverization or suspension liquefaction.

The cosmetic composition may be added by itself or together with other cosmetic ingredients, or may be suitably used according to other conventional methods. Cosmetics include aftershaves, lotions, creams, masks and make-up, but not limited to them.

The cosmetic composition can be formulated into various compositions such as gels, creams, ointments and the like. The composition in the form of a gel, a cream and an ointment can be suitably prepared according to the form of the composition by a known method, by adding a conventional softener, an emulsifier and a thickener or a raw material known in other techniques.

The composition in the form of a gel can be prepared, for example, by adding a softening agent such as trimethylolpropane, polyethylene glycol, and glycerin, a solvent such as propylene glycol, ethanol, and isocetyl alcohol, and pure water.

The composition of the cream form can be prepared, for example, by the addition of fatty alcohols such as stearyl alcohol, stigmasterol, behenyl alcohol, arachidyl alcohol, isostearyl alcohol and isocetyl alcohol; emulsifiers such as lipids , for example, lecithin, phospholipid choline, phospholipid oxime ethanolamine, phospholipid serine, phospholipid inositol and its derivatives, glyceryl stearate, sorbitan palmitate, sorbitan stearate, etc.; natural fat And oils such as avocado oil, almond oil, babass oil, Borage oil, camellia oil, etc.; lipid compositions such as neuropterin, cholesterol, fatty acids, phytosphingosine, lecithin, etc.; solvents such as propylene glycol, etc.; and pure water.

The preparation in the form of an ointment can be prepared, for example, by the addition of softening agents, emulsifiers and waxes, such as microcrystalline waxes, paraffin waxes, ceresins, beeswax, cetyl wax, petrolatum and the like.

In another aspect, the invention provides a method of using the composition to prepare an agent for treating or ameliorating atopic dermatitis. As used herein, the term "treatment or alleviation" is intended to mean the course or symptom of a disease that is stopped or delayed when a patient uses the agent.

Figure 1. Changes in body weight of mice in each group

Figure 2. Changes in mouse ear thickness in each group

Figure 3. Changes in ear weight of each group of mice

Figure 4. Photographs of mouse ears in each group

Figure 5. Tissue section of mouse ears in each group

Figure 6. HPLC chromatogram of mangosteen fruit shell alcohol extract

Example 1: Preparation of a pharmaceutical composition

Take the mangosteen fruit shell, dry the shell to 50%~95%, extract with solvent (such as water or 10%~95% alcohol), and concentrate to obtain mangosteen fruit shell extract.

Separating the outer shell and the inner shell of the mangosteen fruit, and drying the mango shell and the mango shell inner shell to 50%~95%, and extracting with solvent (such as water or 10%~95% alcohol). Concentrated to obtain mangosteen fruit shell extract and mangosteen shell shell extract.

Alcohol and water extracts of mangosteen fruit husks, alcohol and water extracts of mangosteen fruit husks and shells are made into different concentrations of cream or ointment.

Example 2: Animal test

The test animals used 8-week-old BALB/c mice (purchased from Lesco Biotech) and weighed 25 to 28 g. They were quarantined by an animal house veterinarian for one week before entering the breeding room. Animals were divided into 9 groups, 3 in each group, for a total of 27. The breeding room was set at a temperature of 21 ± 2 ° C, a humidity of 30-70%, and a 12-hour bright, 12-hour dark light cycle. Unlimited supply of feed and water.

The animal experiment used 2-Chloro-1,3,5-trinitrobezene (TNCB) to induce atopic dermatitis in mice, using acetone as solvent. TNCB at a concentration of 1% was applied to the ears of mice (1 time/2 days) one week before the test article. The test substance was administered one week later (1 time / 1 day) and the mice were continuously induced with TNCB (1 time / 2 days). In addition, the oral dose was 60 mg/kg and the volume was 10 ml/kg. In the event that the TNCB is administered on the same day as the test article, the TNCB is administered at least one hour apart from the test substance in order to reduce the interaction between the two. The experimental design grouping is shown in the table below.

PO: Oral administration

Mouse body weight changes and ear thickness were monitored twice a week. All experimental animals were subjected to blood collection before and after TNCB induction, before and at the time of sacrifice. The blood was centrifuged at 3,000 rpm for 30 minutes at 4 ° C, and serum was obtained, and the sample was stored.

All animals were sacrificed at the end of the third week after the test article was taken, and the mouse ears were taken and photographed and placed in a 10% formalin solution for pathological section observation. Pathological observations were performed by HE staining (trusted by the National Animal Center to perform histopathological analysis).

Data are expressed as mean ± standard error (SEM) and Student's t-test is used to compare differences between treatment groups. Asterisks indicate significant differences, with p < 0.05 for *; p < 0.01 for **; p < 0.001 for ***.

test results

Body weight: After TNCB induced atopic dermatitis in mice, there was no statistically significant difference in body weight as a whole due to a slight decrease in body weight due to discomfort in the first week after administration of the test substance (Fig. 1).

Ear thickness change: After the mice were given different doses of test ointment after induction, it was observed that the degree of swelling (thickness) of the mouse ear decreased with the dose of the test substance, and the drug of the positive control group (1% acetic acid hydrogenation was observed). The group of Hydrocortisone acetate and high-dose test substance (5%) had an inhibition rate of 52.7% and 47.3%, respectively, compared with the model group (p<0.01) (Table 2, Figure 2).

Table 2, experimental group ear thickness and ear weight inhibition rate (%)

Changes in ear weight after sacrifice: The mouse ears were removed after the end of the experiment and weighed to observe that the weight of the mouse ears gradually decreased as the dose of the test substance increased. In the group administered with the positive control group (1% hydrocortisone acetate) and the high dose test substance (5%), 82.4% and 69.5% inhibition rates were observed compared with the model group (p<0.01). The other 2% and 3% of the test substances also had an inhibition rate of 28.2% and 28.9% (p<0.05), respectively (Table 2, Figure 3).

Appearance of the ears after sacrifice: After the end of the experiment, the ears of the mice were removed to observe the appearance. It was also found that the group of the positive control group (1% hydrocortisone acetate) and the high dose (5%) were given, and the ear contour was intact. The surface dandruff and roughness are also mild (Figure 4).

Histopathological analysis: According to the results of pathological section of the National Experimental Animal Center, the severity of TNCB-induced chronic active dermatitis (Chronic-active Dermatitis) lesions was divided into five levels: very small (level 1), mild (level 2), medium Degree (level 3), moderate severity (level 4) and extreme severity (level 5). The results showed that the average severity of lesions in the solvent control group, 0.5% and 2% was 4.67; the average severity of lesions in the 1% and 2%+PO 60mg/kg group was grade 5; the average severity of 3% was 4.33; positive control The group of drugs (1% hydrocortisone acetate) had an average severity of 3, while the 5% group had an average severity of 2.67 (Table 3, Figure 5).

Analysis of extracts from the inner and outer shells of mangosteen fruit: According to the results of pathological sectioning of the National Experimental Animal Center, the severity of TNCB-induced Chronic-active Dermatitis lesions was divided into five levels: very small (level 1), light Degree (Level 2), Moderate (Level 3), Moderately Serious (Level 4), and Extremely Serious (Level 5). The results show that the outer casing is better than the inner casing (Table 4).

Example 3: Serum analysis

Serum was preserved at the time of sacrifice, and serum biochemical indicators (IL-1β, IL-2, IL-4, were performed according to the manual of the MAGPIX analyzer (Millipore, USA) and the reagent MCYTOMAG analysis kit (Millipore, USA). Analysis of IL-3, IL-5, IL-7, IL-10, IL-12 (p40), IL-15, IL-17, MCP-1, RANTES, TNF-α).

In the atopic dermatitis model, IL-7, IL-10, IL-15 and MCP-1 were significantly increased, while mangosteen fruit husk extracts inhibited the increase of its index. Mangosteen fruit shell The extracts were inhibited by 111.7%, 77.1%, 100%, 24%, and 16.1%, respectively. The inhibitory indexes of mangosteen shell extracts were 97.0%, 92.8%, 65.6%, 82.7%, and 27%, respectively. The results showed that mangosteen husk could inhibit atopic dermatitis by inhibiting immunoregulatory related hormones, but not IL-1 or TNF-α inflammatory related cytokines. For example, the mode of action of similar sterol drugs can inhibit a part of the immune system and thus affect the atopic dermatitis. Under the IL-10 index, the extract of mangosteen shell shell is significantly better than the shell shell extract can completely inhibit IL- 10 indicators, while IL-10 is an important cytokine for TH2 pathway antibodies. Therefore, mangosteen shell extract is different The effect of dermatitis is greater than that of mangosteen husk inner shell extract. In addition, although the mode of action of mangosteen fruit hulls is similar to steroid drugs, steroids can inhibit the production of IL-15 under the index of IL-15, while mangosteen shells have a significant effect. This evidence shows that mangosteen The effect of the shell extract is specific to steroids rather than to the overall immune system. It can be seen that the composition and mechanism of action of mangosteen shell extract and inner shell extract are not exactly the same.

As is apparent from the results of the above examples, the composition of the present invention has a remarkable effect on atopic dermatitis.

Example 4: High Performance Liquid Chromatography Analysis of Mangosteen Fruit Shell Alcohol Extract

The chemical fingerprints of mangosteen fruit shell alcohol extracts were analyzed by high performance liquid chromatography (HPLC). Weigh the mangosteen fruit shell alcohol extract 300mg±1mg into a 100mL dosing bottle, dilute to 100mL with Diluent, and then oscillate with ultrasound for at least 60min until completely dissolved, then let stand at room temperature and return to temperature. After the bottom oil was evenly mixed, 2 mL of the solution was taken out from a 100 mL dosing bottle and transferred into a 20 mL dosing bottle, and the solution was adjusted to a volume of 20 mL with a diluent (Diluent), and then filtered through a 0.45 μm PVDF filter.

High performance liquid chromatography (HPLC) analysis was performed using an AGILENT/1100 series HPLC system equipped with a PDA detector and an autosampler. The column column (COSMOSIL MS-II, 5 um, 4.6 x 250 mm, Waters) was maintained at 30 ° C during the analysis. 10 μL of the sample was injected into the HPLC system. Chemical fingerprinting was performed using an acetonitrile-water-0.2% phosphoric acid eluent system (ACN/H ₂ O=72/28 (v/v), w/0.2% H ₃ PO ₄ ) at a flow rate of 1.0 ml/min. The detection wavelength was UV 240 nm for peak detection. Figure 6 shows the HPLC fingerprinting analysis of mangosteen fruit shell alcohol extract. The results showed that the mangosteen fruit shell alcohol extract had the following HPLC peaks for retention time (Table 6).

Claims (10)

Use of a composition for the manufacture of a medicament for the treatment of a skin condition, wherein the composition comprises an effective amount of mangosteen husk extract. The use according to claim 1, wherein the mangosteen fruit shell extract is mangosteen fruit shell water extract and/or mangosteen fruit shell alcohol extract. The use according to claim 1, wherein the mangosteen husk is a mangosteen shell and/or a mangosteen shell. The use according to claim 1, wherein the mangosteen husk is a mangosteen shell. The use according to claim 1, wherein the mangosteen husk extract comprises α-mangostin and γ-mangostin. The use of claim 1, wherein the composition further comprises an excipient having a ratio of from 1% to 10%. The use of claim 1, wherein the composition inhibits an increase in IL-7, IL-10, IL-15 or MCP-1. The use of claim 1, wherein the composition is a parenteral preparation. The use according to claim 8, wherein the parenteral preparation is an external preparation. The use of the invention of claim 1, wherein the skin disease is atopic dermatitis.