KR20150071968A - Composition for inhibition of sebum, and/or prevention or improving of acne skin disease comprising artemisinic acid, its derivatives or cosmetically or pharmaceutically acceptable salts thereof - Google Patents

Abstract

The present invention relates to a composition for preventing or improving acne skin disease and/or inhibiting sebum including an artemisinic acid, derivative thereof or cosmetically or pharmaceutically acceptable salt wherein the artemisinic acid, derivative thereof or cosmetically or pharmaceutically acceptable salt of the composition can inhibit propionibacterium acnes and creation of inflammatory materials from propionibacterium acnes while reducing creation of sebum from sebum cells and can be safely used in cosmetic materials and pharmaceutical composition because the composition has no toxicity and side effects for skin.

Description

TECHNICAL FIELD The present invention relates to a composition for preventing or ameliorating sebum-inhibiting and / or acne skin diseases, which comprises atemic acid, its derivatives or a cosmetic or pharmaceutically acceptable salt thereof. of acne skin disease comprising < RTI ID = 0.0 > artemisinic < / RTI > acid, its derivatives or cosmetically or pharmaceutically acceptable salts thereof,

The present invention relates to a composition for preventing or ameliorating sebum and / or acne skin diseases. More particularly, the present invention relates to a composition for preventing or ameliorating skin diseases, And a composition for preventing or ameliorating sebum inhibiting and / or acne skin diseases, which comprises atemic acid, derivatives thereof, or a cosmetic or pharmaceutically acceptable salt thereof, which is excellent in an effect of inhibiting sebum production.

Acne is an inflammatory skin disease that occurs in the skin of hair follicles. Although it is known to be a juvenile disease that occurs mostly in adolescents, the incidence of acne in adults is increasing recently. Specifically, the incidence of acne in adolescents aged 12 to 24 is 70% to 87%, and the incidence of acne in adults aged 25 to 34 is 8%, but acne occurs in 3% of adults aged 35 to 44 (Ahn, 2006), Acne Bible Diagnosis and Treatment). Direct causes of acne are known as male hormones, and indirect causes include stress, smoking, food, and cosmetics. Testosterone, which is known to be a direct cause of acne, promotes sebaceous secretion by stimulating the sebaceous glands and promotes the thickening of the pore wall keratin, which causes the pores to clog and cause sebum discharge. Propionibacterium acnes , also known as acne bacterium, produces free fatty acids by decomposing sebum fat, which is present in the hair follicles but is not released into the skin. At this time, the free fatty acid produced by acne bacteria and the enzyme secreted directly induces inflammation in the hair follicle, which deepens the symptoms. The quality of life of patients with acne was significantly worse than that of patients with single lesions such as epidermoid cysts and biliary keratosis, and the quality of life was similar to that of patients with psoriasis (Ahn, Bong- (2004) Korean Journal of Dermatology 43: 6-14).

Drugs used in the treatment of acne now have a bactericidal effect and inhibit the local application of antibiotics such as clindamycin, tetracycline and erythromycin, which inhibit the production of free fatty acids, acne proliferation and inflammatory responses (Retinoid), which is a modified form of vitamin A, has been used. However, when the acne remedy is used for a long period of time, there is a problem such as a bad feeling due to a salt, hypertriglyceridemia and tolerance.

In order to solve the above problems, there is a wide search for acne remedies for plant extracts, which are known to have less side effects than a single substance. Typical examples of this are ash, tea trioyl, green tea, rooibos, and aloe. However, in the case of such plant extracts, the effective concentration of the substance showing efficacy is weak, and the effect of acne symptoms triggered by various routes is not shown.

On the other hand, artemisinic acid and its derivative dihydroartemisinic acid are precursors of artemisinin, a typical anti-malarial therapeutic agent derived from Artemisia annua L , Or by microbial cultivation. Atemic acid and dihydroatomic acid have been actively studied for their role as precursors in the production of atemicinin, and antifungal and anticancer effects have been reported (Galal AM et al. , J Nat Prod , 68 (6), 2005, Sun WC et al ., Zhongguo Yao Li Xue Bao, 13 (6), 1992). However, the inhibition of sebum production and the improvement of acne skin disease in these substances have not been reported.

Accordingly, the present inventors have developed a therapeutic composition effective against acne occurring in various pathways by selecting substances exhibiting an inhibitory effect on acne bacterium growth, an inflammation inhibitory effect by acne bacteria, and an inhibitory effect on sebum production in a phytochemical derived from plant extract As a result, it has been confirmed that atemic acid, a derivative thereof, or a cosmetically or pharmaceutically acceptable salt thereof is effective in inhibiting sebum production and treating acne skin diseases, thus completing the present invention.

Accordingly, one object of the present invention is to provide a composition for preventing or ameliorating sebum-inhibiting and / or acne skin diseases comprising atemic acid, a derivative thereof, or a cosmetic or pharmaceutically acceptable salt thereof .

It is another object of the present invention to provide a cosmetic or pharmaceutical composition for preventing or ameliorating skin sebum and / or acne skin diseases comprising the composition as an active ingredient.

The present invention relates to a composition for preventing or ameliorating sebum-suppressing and / or acne skin diseases comprising artemisinic acid, a derivative thereof, or a cosmetic or pharmaceutically acceptable salt thereof.

The artemisinic acid of the present invention is an artemisinin derivative. The IUPAC name is 2 - [(4R) -4,7-dimethyl-1,2,3,4,4a, 5,6,8a- octahydronaphthalen-1-yl] prop-2-enoic acid.

In the present invention, the derivative of athemic acid is, for example, dihydroartemisinic acid, and its IUPAC name is (2R) -2 - [(1R, 4R, 4aS, 8aS) 7-Dimethyl-1,2,3,4,4a, 5,6,8a-octahydro-1-naphthalenyl] propanoic acid.

The atemic acid or derivative thereof may be extracted, separated and purified from Artemisia annua L or obtained by culturing microorganisms such as Saccharomyces cerevisiae or chemically synthesized products For example, artemisinic acid from Sami Labs Limited or dihydroartemisinic acid from Xi'an Tian Ben Bio-Engineering Co.).

When the atemic acid or its derivative of the present invention is extracted from a plant, it can be extracted using an extraction solvent. The extraction solvent is water, an anhydrous or a lower alcohol having 1 to 4 carbon atoms (methanol, ethanol, propanol, ), Acetone, ethyl acetate, chloroform, and 1,3-butylene glycol, alone or in combination of two or more, is preferably used, but not always limited thereto.

In addition, the atemic acid or derivative thereof can be obtained through a conventional purification process in addition to the extraction method using the extraction solvent. For example, by separation using an ultrafiltration membrane having a constant molecular weight cut-off value, separation by various chromatographies (made for separation by size, charge, hydrophobicity or affinity), and the like, Atemic < / RTI > acid or derivatives thereof can also be obtained through fractionation.

In the present invention, the atemic acid or a derivative thereof may be used in the form of a cosmetically or pharmaceutically acceptable salt. Such salts include those formed by acid addition salts or bases formed by cosmetically or pharmaceutically acceptable free acids. As examples of the free acid, inorganic acids and organic acids can be used. As the inorganic acids, hydrochloric acid, sulfuric acid, bromic acid, sulfurous acid or phosphoric acid can be used. As the organic acids, citric acid, acetic acid, maleic acid, fumaric acid, Methanesulfonic acid and the like can be used. As the metal salt, an alkali metal salt or an alkaline earth metal salt, sodium, potassium or calcium salt may be used. But is not necessarily limited thereto.

Since the composition of the present invention has an effect of inhibiting the production of sebum at the cell site, which is a sebum-producing cell, it has a sebum suppressing purpose.

The composition for suppressing sebum may be applied to various sebum-related diseases, diseases or abnormal conditions which can be prevented or treated by inhibiting or eliminating the production of sebum. Sebum-related diseases that can be prevented or treated by the composition of the present invention include, but are not limited to, acne, seborrheic dermatitis, dermatitis in situ, red nose, blackhead and stain.

In addition, the composition of the present invention has a use for preventing or ameliorating acne skin diseases. As one example, the atemic acid or dihydroartemic acid of the present invention inhibits the growth of P. acnes , one of the acne bacteria, and inhibits the growth of P. acnes , (IL-8) and tumor necrosis factor (TNF-a) involved in the inflammatory response, thereby preventing, ameliorating or treating acne skin diseases. Lt; / RTI >

In the present invention, the atemic acid or a derivative thereof or a cosmetic or pharmaceutically acceptable salt thereof may be contained in an amount of 0.0001 to 10% by weight, preferably 0.0001 to 5% by weight, based on the total weight of the composition have. When the content is less than 0.0001% by weight, the effect of inhibiting sebum formation and treating, preventing and improving acne is too weak. When the content is more than 10% by weight, the effect is not increased with increasing content, There is a problem.

As used herein, the term "prophylactic " means inhibiting the occurrence of a disease or disorder in an individual who has never been diagnosed as having a disease or condition, but is likely to be susceptible to such disease or disease. Also, as used herein, the term " improvement "or" treatment "means (a) inhibiting the development of a disease or disease in an individual, (b) relieving the disease or disorder and (c) As used herein, the term "individual" means a mammal, including a human, having a disease whose symptoms may be ameliorated by administration of the composition of the present invention, such as a monkey, cow, horse, pig, sheep, dog, cat, rat, Means a mammal.

As one specific use of the present invention, the composition of the present invention may be manufactured from a cosmetic composition or a pharmaceutical composition.

When the composition of the present invention is a cosmetic composition, it may contain ingredients conventionally used in cosmetic compositions in addition to the atemic acid, derivatives thereof, or cosmetically acceptable salts thereof. For example, conventional auxiliaries acceptable as cosmetics such as antioxidants, stabilizers, solubilizers, vitamins, pigments and perfumes, and carriers.

The cosmetic composition may be formulated into a solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant-containing cleansing oil, powder foundation, emulsion foundation, wax foundation, But is not limited thereto. More specifically, it may be formulated into a nutritional cream, a convergent lotion, a soft lotion, a lotion, an essence, a shampoo, a nutritional gel or a massage cream.

Starch, tragacanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide as the carrier component when the cosmetic composition is a paste, cream or gel, Can be used.

When the formulation of the cosmetic composition is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component. In particular, in the case of spray, a mixture of chlorofluorohydrocarbons, Propane / butane or dimethyl ether.

When the cosmetic composition is a solution or an emulsion, a solvent, a dissolving agent or an emulsifying agent is used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, 3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol or fatty acid esters of sorbitan, and the like.

When the formulation of the cosmetic composition is in the form of a suspension, the carrier component may be a liquid diluent such as water, ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, Cellulose, aluminum metahydroxide, bentonite, agar or tragacanth.

When the formulation of the cosmetic composition is an interfacial active agent-containing cleansing, it is preferable to use, as carrier components, aliphatic alcohol sulfates, aliphatic alcohol ether sulfates, sulfosuccinic acid monoesters, isethionates, imidazolinium derivatives, methyltaurates, sarcosinates, fatty acids Amide ether sulfate, alkylamidobetaine, aliphatic alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, lanolin derivative, or ethoxylated glycerol fatty acid ester.

When the composition of the present invention is a pharmaceutical composition, it may contain a pharmaceutically acceptable carrier, excipient and diluent in addition to the atemic acid, a derivative thereof or a pharmaceutically acceptable salt thereof. The pharmaceutically acceptable carriers to be contained in the pharmaceutical composition of the present invention are those conventionally used in the present invention and include carbohydrate-based compounds such as lactose, amylose, dextrose, sucrose, sorbitol, mannitol, starch, cellulose, etc. ), Acacia gum, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, salt solution, alcohol, gum arabic, vegetable oil But are not limited to, vegetable oils, soybean oil, soybean oil, olive oil, coconut oil), polyethylene glycol, methylcellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. The pharmaceutical composition of the present invention may further contain a lubricant, a wetting agent, a sweetening agent, a flavoring agent, an emulsifying agent, a suspending agent, a preservative, etc. in addition to the above components. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington ' s Pharmaceutical Sciences (19th ed., 1995).

The pharmaceutical composition of the present invention may be administered orally or parenterally to mammals such as rats, mice, livestock, humans, and the like, and all manner of administration may be expected, for example, oral, rectal or intravenous, May be administered by subcutaneous injection. At this time, transdermal administration is preferable for the parenteral route, and local application is most preferable.

The appropriate dosage of the pharmaceutical composition of the present invention may vary depending on factors such as the formulation method, administration method, age, body weight, sex, pathological condition, food, administration time, administration route, excretion rate, . On the other hand, the dosage of the pharmaceutical composition of the present invention is preferably 0.1-100 mg / kg (body weight) per day. When the composition is an external preparation, it is preferable to apply the composition in an amount of 1.0 to 3.0 ml on an adult basis once to five times a day for one month or longer. However, the dose is not intended to limit the scope of the present invention.

The pharmaceutical composition of the present invention may be formulated into a unit dose form by formulating it using a pharmaceutically acceptable carrier and / or excipient according to a method which can be easily carried out by a person having ordinary skill in the art to which the present invention belongs. Or by intrusion into a multi-dose container. The formulations may be in the form of solutions, suspensions, syrups or emulsions in oils or aqueous media, or in the form of excipients, powders, powders, granules, tablets or capsules, and may additionally contain dispersing or stabilizing agents.

On the other hand, as a result of a skin irritation test for the atemic acid, its derivative or a cosmetic or pharmaceutically acceptable salt thereof of the present invention, atemic acid, a derivative thereof or a cosmetic or pharmaceutically acceptable salt thereof, And there is little side effect. Therefore, it can be used safely even in long-term use, and in particular, it can be applied to cosmetic and pharmaceutical compositions as described above.

The atemic acid, its derivatives, or a cosmetic or pharmaceutically acceptable salt thereof of the present invention inhibits the growth of acne bacterium, inhibits the production of inflammatory substances produced from acne bacterium, inhibits sebum production from sebaceous cells Effect. In addition, it can be safely applied to cosmetic and pharmaceutical compositions without cytotoxicity and skin side effects.

Figure 1 shows the results of measuring the minimal bactericidal concentration (MBC) of atemic acid or dihydroartemic acid against Propionibacterium acnes .

Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these embodiments are only for describing the present invention in more detail and that the scope of the present invention is not limited by these embodiments in accordance with the gist of the present invention .

Example 1: Propionibacterium acnes of atemic acid or dihydroatomic acid ( Propionibacterium acnes ) To measure antimicrobial activity against

1-1. Determine minimum inhibition concentration (MIC)

In order to activate the P. acnes , 3 ml of BHI broth (3.7%) was incubated at 37 ° C in an anaerobic incubator for 48 hours. The culture broth was transferred to a BHI solid medium Brain-Heart infusion broth (3.7%; agar 1.5%). Then, 100 μg / ml of a mixture of athemic acid (ChemFaces, China) and dihydroartemic acid (ChemFaces, China) was dispensed on a 10 mm paper disk, and the mixture was placed on the solid medium and incubated in a 37 ° C. anaerobic incubator for 24 hours And the presence of inhibition zone was confirmed. The minimum inhibition concentration (MIC) of atemic acid or dihydroartemic acid was determined by the two-fold serial dilution method. Here, MIC is defined as the minimum concentration that inhibits the growth of microorganisms. The results are shown in Table 1.

Atemic acid Dihydroartemic acid MIC concentration 500 μM 250 μM

As a result of the experiment, it was confirmed that the MIC concentrations of atemic acid or dihydroatomic acid for Propionibacterium acnes were 500 μM and 250 μM, respectively.

1-2. The minimal bactericidal concentration (MBC)

To activate P. acnes , the cells were cultured in a 3 ml BHI liquid medium (Brain heart infusion broth: 3.7%) at 37 ° C in an anaerobic incubator so as to have a cell number of 1 × 10 ⁵ cells, Were plated in 0.1 ml of BHI solid medium (Brain-Heart infusion broth; 3.7%; agar 1.5%) and cultured for 48 hours. Then the viable cell count on the solid medium was measured. Here, MBC is defined as the minimum concentration at which colony can not be generated. The results are shown in Fig.

As a result of the experiment, it was confirmed that MBC concentrations of atemic acid or dihydroartemic acid for Propionibacterium acnes were 750 쨉 g / ml and 500 쨉 g / ml, respectively.

Example 2: Propionibacterium acnes of atemic acid or dihydroatomic acid ( Propionibacterium acnes ) To measure anti-inflammatory activity

Human monocyte cells (THP-1, Korean Cell Line Bank) were inoculated into a 24-well microplate containing RPMI-1040 medium without FBS (about 1 x 10 ⁶ cells per well) And a 5% CO ₂ concentration Lt; RTI ID = 0.0 > 37 C < / RTI > for 24 hours. Then, 10 μg / ml of propionibacterium acnes, atemic acid (ChemFaces, China) and dihydroartemic acid (ChemFaces, China) were treated with 10 and 100 μM, respectively, and then re-cultured for 48 hours , And the cell culture medium was collected to prepare a sample.

Interleukin-8 (IL-8) and Tumor necrosis factor-alpha (TNF-alpha) system were used for the anti-inflammatory activity of the samples prepared above. (R & D, Minneapolis MN, USA) using an ELISA kit (Genzyme, Mineapolis, MN) with an antibody of interleukin-8 (IL-8) and tumor necrosis factor (TNF- IL-8) and tumor necrosis factor (R & D, Minneapolis MN, TNF-alpha). As a control, mononuclear cells not treated with propionibacterium acnes, atemic acid or dihydroartemic acid were used. The results are shown in Table 2.

% of cont IL-8 TNF-alpha P. acne Untreated Control group 54 61 P. acne 100 [mu] g / ml treated group Control group 100 100 Atemic acid 10 μM 95 90 Atemic acid 100 μM 65 67 Dihydroartemic acid 10 [mu] M 97 83 Dihydroartemic acid 100 [mu] M 70 64

As a result of the experiment, the atemic acid or dihydroatomic acid inhibits the production of IL-8 and TNF-alpha induced by propionibacterium acnes, and the higher the concentration of atemic acid or dihydroartemic acid, -8 and TNF-alpha, indicating that there is a tendency to be concentration-dependent.

Example 3: Test for inhibiting sebum production of sebum cells of atemic acid or dihydroartemic acid

Commercially available sebocyte cells (PromoCell, USA) were purchased and cultured. The cells were seeded at a density of 1 × 10 ⁵ cells / ml in a 24-well plate and seeded with cell differentiation medium (50 ug / ml BPE (bovine pituitary extract), 1 mg / ml faf- BSA (fatty acid-free bovine serum albumin) 10 and 100 μM of DMEM: F12 (1: 1) supplemented with 10 μg / ml linoleic acid (LIN)) and atemic acid (ChemFaces, China) and dihydroartemic acid (ChemFaces, China) Lt; / RTI > After culturing for 3 days, the cells were treated with nile red dye for staining fat, and the extent of fat accumulation was observed by FASC analysis. As a control group, cell-site cells not treated with atemic acid or dihydroartemic acid were used. The results are shown in Table 3.

Fluorescence intensity (Nile red) Control group 103 Atemic acid 10 μM 98 Atemic acid 100 μM 52 Dihydroartemic acid 10 [mu] M 95 Dihydroartemic acid 100 [mu] M 71

Experimental results showed that the degree of fat accumulation decreased when atemic acid or dihydroartemic acid was treated. Also, as the concentration of atemic acid or dihydroartemic acid increased, the degree of fat accumulation decreased.

Example 4: Confirmation of safety of human skin of atemic acid or dihydroartemic acid

4-1. Production of external skin preparation containing atemic acid or dihydroartemic acid

In order to confirm that atemic acid or dihydroartemic acid is safe for human skin, a skin external preparation containing atemic acid or dihydroartemic acid was prepared by the ingredients and contents shown in Table 4, Respectively. First, purified water, glycerin, and butylene glycol were mixed and dissolved at 70 캜 (water part), and the other components except for the above three components and trimethanolamine were dissolved at 70 캜 (oil part). The oil part was added to a water part and stirred with a homomixer (Tokushu Kika, Japan) for primary emulsification, and trimethanolamine was finally added thereto. Next, the bubbles generated in the mixed solution were removed, and the mixture was cooled to room temperature to prepare an external preparation for skin.

ingredient content (%) Control group Test group 1 Test group 2 Purified water 72 72 72 glycerin 8.0 8.0 8.0 Butylene glycol 4.0 4.0 4.0 Atemic acid 0 1.0 0 Dihydroartemic acid 0 0 1.0 Caprylic Capri Triglyceride 8.0 8.0 8.0 Squalane 5.0 5.0 5.0 Cetearyl glucide 1.5 1.5 1.5 Sorbitan stearate 0.4 0.4 0.4 Cetearyl alcohol 1.0 1.0 1.0 Trimethanolamine 0.1 0.1 0.1 Gross weight 100 100 100

4-2. Experiment of cumulative stimulation of skin

The skin external preparation prepared by the method of 4-1 above was applied to 30 healthy adults for 9 times and 24 hours cumulative pelletization on the upper forearm every other day to determine whether atemic acid or dihydroartemic acid stimulates the skin Were measured. As a control group, a skin external preparation containing no atemic acid or dihydroartemic acid as a squalane base was used.

A pin chamber (Finn chamber, Epitest Ltd, Finland) was used as a coating method, and 15ul of each skin external agent was dropped into the chamber, followed by applying a patch. The degree of the skin reaction on each occasion was scored using Equation 1 below, and the results are shown in Table 5 below.

[Experimental Equation 1]

The number of tests (9 times) and the number of tests (9 times)

At this time, a score of ± is given as 1, a score of 2 is given as +, and a score of 4 is given as ++, and a safe composition is judged when the average degree of reaction is less than 3.

Test substance Number of subjects who responded (persons) Average
Reactivity 1 week 2 weeks 3 weeks Primary Secondary Third Fourth 5th 6th Seventh 8th car 9th ± / + / ++ ± / + / ++ ± / + / ++ ± / + / ++ ± / + / ++ ± / + / ++ ± / + / ++ ± / + / ++ ± / + / ++ Control group 0/-/- - / - / - - / - / - - / - / - - / - / - - / - / - - / - / - - / - / - - / - / - 0.00 Test group 1 One/-/- 0/-/- - / - / - - / - / - - / - / - - / - / - - / - / - - / - / - - / - / - 0.09 Test group 2 0/-/- 0/-/- - / - / - - / - / - - / - / - - / - / - - / - / - - / - / - - / - / - 0.00 Subject 30 30 30 30 30 30 30 30 30

As a result of the test, the number of persons corresponding to ±, +, and ++ in test group 1 was 0, 1, and 0, respectively. When calculated according to the above-described formula, the average reactivity of Test Groups 1 and 2 was 0.09, 0.00, which was 3 or less. These results indicate that the external preparation for skin including atemic acid or dihydroartemic acid (test group 1 or test group 2) did not exhibit a clear cumulative stimulation pattern and was judged to be a skin-safe substance.

Formulation Example 1: Formulation of cosmetic preparation

1-1. Production of flexible lotion

As shown in the following Table 6, a soft lotion containing an atemic acid or dihydroartemic acid extract as an active ingredient was prepared by a conventional method.

ingredient Content (% by weight) Atemic acid or dihydroartemic acid 0.01 glycerin 3.0 Butylene glycol 2.0 Propylene glycol 2.0 Carboxyvinyl polymer 0.1 ethanol 10.0 Triethanolamine 0.1 Preservatives, micronutrients, trace fragrances and trace water Balance sum 100.0

1-2. Manufacture of nutrition lotion

As shown in Table 7 below, a nutrition lotion containing atemic acid or dihydroartemic acid as an active ingredient was prepared according to a conventional method.

ingredient Content (% by weight) Atemic acid or dihydroartemic acid 0.01 Wax 4.0 Polysorbate 60 1.5 Sorbitan sesquioleate 0.5 Liquid paraffin 5.0 Squalane 5.0 Caprylic / capric triglyceride 5.0 glycerin 3.0 Butylene glycol 3.0 Propylene glycol 3.0 Carboxyvinyl polymer 0.1 Triethanolamine 0.2 Preservatives, micronutrients, trace fragrances and trace water Balance sum 100.0

1-3. Manufacture of nutrition cream

A nutritional cream containing atemic acid or dihydroartemic acid as an active ingredient was prepared according to a conventional method as shown in Table 8 below.

ingredient Content (% by weight) Atemic acid or dihydroartemic acid 0.01 Wax 10.0 Polysorbate 60 1.5 Sorbitan sesquioleate 0.5 Liquid paraffin 10.0 Squalane 5.0 Caprylic / capric triglyceride 5.0 glycerin 5.0 Butylene glycol 3.0 Propylene glycol 3.0 Triethanolamine 0.2 Preservatives, micronutrients, trace fragrances and trace water Balance sum 100.0

1-4. Manufacture of massage cream

A massage cream containing atemic acid or dihydroartemic acid as an active ingredient was prepared according to a conventional method as shown in Table 9 below.

ingredient Content (% by weight) Atemic acid or dihydroartemic acid 0.01 Wax 10.0 Polysorbate 60 1.5 Sorbitan sesquioleate 0.8 Liquid paraffin 40.0 Squalane 5.0 Caprylic / capric triglyceride 4.0 glycerin 5.0 Butylene glycol 3.0 Propylene glycol 3.0 Triethanolamine 0.2 Preservatives, micronutrients, trace fragrances and trace water Balance sum 100.0

1-5. Manufacture of packs

As shown in Table 10 below, a pack containing athemic acid or dihydroartemic acid as an active ingredient was prepared according to a conventional method.

ingredient Content (% by weight) Atemic acid or dihydroartemic acid 0.01 Polyvinyl alcohol 13.0 Sodium carboxymethylcellulose 0.2 Allantoin 0.1 ethanol 5.0 Nonyl phenyl ether 0.3 Preservatives, micronutrients, trace fragrances and trace water Balance sum 100.0

Preparation Example 2: Preparation of pharmaceutical preparations

2-1. Manufacture of Powder

In order to prepare powders containing atemic acid or dihydroartemic acid as an active ingredient, the ingredients shown in the following Table 11 were mixed and filled in airtight bags to prepare powders.

ingredient Content (g) Atemic acid or dihydroartemic acid 2 Lactose One

2-2. Manufacture of tablets

In order to prepare tablets containing atemic acid or dihydroartemic acid as an active ingredient, tablets were prepared by mixing the ingredients shown in the following Table 12 and then tableting according to a conventional method for producing tablets.

ingredient Content (mg) Atemic acid or dihydroartemic acid 100 Corn starch 100 Lactose 100 Magnesium stearate 2

2-3. Preparation of capsules

In order to prepare capsules containing atemic acid or dihydroartemic acid as an active ingredient, the ingredients shown in the following Table 13 were mixed and filled in gelatin capsules according to the conventional preparation method of capsules to prepare capsules .

ingredient Content (mg) Atemic acid or dihydroartemic acid 100 Corn starch 100 Lactose 100 Magnesium stearate 2

Claims (6)

A cosmetic composition for prevention or improvement of sebum inhibitory or acne skin diseases, which comprises atemic acid, a derivative thereof or a cosmetically acceptable salt thereof as an active ingredient.
The cosmetic composition according to claim 1, wherein the derivative of atemic acid is dihydroatomic acid.
The cosmetic composition according to claim 1, wherein the atemic acid, a derivative thereof, or a pharmaceutically acceptable salt thereof is contained in an amount of 0.0001 to 10% by weight based on the total weight of the cosmetic composition.
A pharmaceutical composition for the prevention or amelioration of sebum suppression or acne skin diseases, which comprises atemic acid, a derivative thereof or a pharmaceutically acceptable salt thereof as an active ingredient.
5. The pharmaceutical composition according to claim 4, wherein the derivative of athemic acid is a dihydroatomic acid.
5. The pharmaceutical composition according to claim 4, wherein the atemic acid, a derivative thereof, or a pharmaceutically acceptable salt thereof is contained in an amount of 0.0001 to 10% by weight based on the total weight of the pharmaceutical composition.

Images