KR101492706B1 - Compositions for prevention and treatment of obesity and/or lipid-related metabolic disease comprising of dihydroartemisinic acid or pharmaceutically, cosmetically or food acceptable salt thereof as an active ingredient - Google Patents

Abstract

The present invention relates to a composition for the prevention and treatment of obesity and / or lipid-related metabolic diseases comprising dihydroartemisinic acid or a pharmaceutical, cosmetic or pharmacologically acceptable salt thereof as an active ingredient. The composition of the present invention is useful for prevention, treatment and improvement of lipid-related metabolic diseases such as obesity, type 2 diabetes, hyperlipidemia, cardiovascular disease and arteriosclerosis, which are caused by excessive lipid accumulation by blocking lipid differentiation process of immature fat cells It can be safely applied to medicines, cosmetics and functional foods.

Description

TECHNICAL FIELD The present invention relates to a composition for preventing and treating obesity and / or lipid-related metabolic diseases, which comprises dihydroartemic acid or a pharmaceutical, cosmetic or pharmacologically acceptable salt thereof as an active ingredient. lipid-related metabolic disease comprising dihydroartemisinic acid or pharmaceutically, cosmetically or food acceptable salt thereof as an active ingredient}

The present invention relates to a composition useful for the prevention and treatment of obesity and / or lipid-related metabolic diseases, including dihydroatomic acid or its pharmaceutical, cosmetic or pharmacologically acceptable salts.

According to the World Health Organization (WHO) data released in September 2006, there are about 400 million people in the world over the age of 15 who are classified as obese, and over 1.6 billion people are overweight. According to this trend, obesity is becoming a serious social problem, not a simple disease of an individual.

Obesity is a chronic disease that occurs when excess calories are consumed in excess of the calories consumed, resulting in the accumulation of extra calories in the body in the form of fat, or the ability to control energy balance due to lapatin resistance and insulin resistance. , JAMA, 282, 1999), which is a strong risk factor for ischemic heart disease and cerebrovascular disease (Kopleman PG, Nature, 404, 2000; Manson et al., New England J. Med., 333, ).

The causes of obesity are known to be caused by genetic influences, environmental effects of westernized eating habits, and psychological effects due to stress, but the precise cause and mechanism of obesity is unclear.

In addition, fat stored in adipocytes is used as an important energy source in the body, but as the obesity proceeds, the number of adipocytes is increased and the adipocyte differentiation is achieved. Fatty cell differentiation leads to increased triglyceride (triglyceride) synthesis. Neutral fat stored in fat cells increases the size of adipocytes, which can grow up to about 20 times in diameter depending on fat storage, resulting in a cell volume increase of several thousand times. However, since the process of differentiation of new precursor adipocytes into adipocytes is ineffective in controlling diets, in order to control the fundamental treatment or inhibition of obesity, the differentiation process of adipocytes Is important.

The goal of treating obesity, which is caused by such causes and effects, can be divided into two major categories. The first is to burn excess fat to reduce body weight, and the second is to improve metabolic imbalance. Currently, obesity treatment aims not only to lose weight, but also to improve metabolic abnormalities by eliminating factors that cause early cardiovascular disease. In addition, studies to suppress obesity through controlling dietary intake and energy consumption have been actively conducted. The hypothalamus, especially the hypothalamus, plays an important role in the pathogenesis of obesity. Neuropeptide Y, POMC / CART, melanocyte, melanocyte, Cholinesterase, norepinephrine, serotonin, etc. are secreted from the hypothalamus. Current strategies for the development of obesity therapies are such as reducing food intake, inhibiting the absorption of heat, promoting exothermic reactions, regulating energy metabolism, and regulating signaling through the nervous system (MJ Jung, J Pediatr 48 (2), 2005).

The most common drugs include Xenical (Xenical ^TM, Roche Pharmaceuticals, Switzerland), rideoktil (Reductil ^TM, Abbott, USA), exo Rize (Exolise ^TM, Ato Pharma, France), etc. Although heart disease among known obesity treatment so far , Respiratory diseases, and neurological diseases, and the persistence of its efficacy is low, so that the search for anti-obesity substances having safer and superior efficacy is proceeding.

Dihydroartemisinic aicd is a precursor of Artemisinin, a typical anti-malarial drug derived from Artemisia annua L , and may be isolated from mugwort or produced by microbial culture. Dihydro athemic acid has been actively studied for its role as a precursor in the production of atemicinin and it has been known that atemicinin has the efficacy of antimicrobial, anti-cancer, anti-obesity, anti-inflammatory effects (Galal AM et al , J Nat Prod, 68 (6), 2005, Sun WC et al., Zhongguo Yao Li Xue Bao, 13 (6), 1992).

Accordingly, the present inventors have completed the present invention as a result of efforts to develop a single substance which is excellent in prevention and treatment of obesity and lipid-related metabolic diseases, has high stability, and has no skin side effects.

One object of the present invention is to provide a composition for prevention and treatment of obesity and / or lipid-related metabolic diseases comprising dihydroartemisinic acid or a pharmaceutical, cosmetic or pharmacologically acceptable salt thereof as an active ingredient .

Another object of the present invention is to provide a pharmaceutical composition for the prevention and treatment of obesity and / or lipid-related metabolic diseases comprising dihydroartemisinic acid or a pharmaceutically acceptable salt thereof as an active ingredient will be.

It is still another object of the present invention to provide a cosmetic composition for preventing and treating obesity and lipid-related metabolic diseases, which comprises dihydroartemisinic acid or a cosmetically acceptable salt thereof as an active ingredient.

Another object of the present invention is to provide a functional food composition for preventing and improving obesity and / or lipid-related metabolic diseases comprising dihydroartemisinic acid or a pharmaceutically acceptable salt thereof as an active ingredient .

As one embodiment of the present invention, the present invention relates to a composition for preventing and treating obesity and / or lipid-related metabolic diseases comprising dihydroartemic acid or a pharmaceutical, cosmetic or pharmacologically acceptable salt thereof as an active ingredient .

In the present invention, the dihydroartemisinic acid is an artemisinin derivative. The IUPAC name is (2R) -2 - [(1R, 4R, 4aS, 8aS) -4,7-Dimethyl- , 2,3,4,4a, 5,6,8a-octahydronaphthalen-1-yl] propanoated.

The dihydroartemic acid can be extracted, separated and purified from Artemisia annua L or obtained by culturing microorganisms such as Saccharomyces cerevisiae or chemically synthesized products (for example, Xi'an Tian Ben dihydroartemisinic acid of Bio-Engineering Co.). In addition, the dihydroatomic acid may be a reduced atemic acid.

In the present invention, the pharmaceutically, cosmetically or pharmacologically acceptable salts of the dihydroartemic acid include acid addition salts formed by pharmaceutical, cosmetically or pharmacologically acceptable free acids, Metal salts formed by bases are useful. As an example 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. Examples of the organic acids include citric acid, acetic acid, maleic acid, fumaric acid, Sulfonic 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.

In the present invention, obesity means a condition or disease having excessive body fat due to energy imbalance.

In the present invention, a lipid-related metabolic disease refers to a disease caused by excessive lipid accumulation in vivo. Specific examples include diabetes, hypertension, stroke, hyperlipidemia, arteriosclerosis, and cardiovascular disease.

In the present invention, prevention means any action that inhibits or delays the invention of obesity by administration of the composition. Further, the term, improvement, or treatment used in the present invention means all actions in which excess body fat due to obesity is reduced or changed by administration of the composition.

In the present invention, a composition for the prevention and treatment of obesity and lipid-related metabolic diseases comprising dihydroartemic acid or a pharmaceutical, cosmetic or pharmacologically acceptable salt thereof as an active ingredient reduces the body fat content, Reduce the content of fat, prevent absorption and digestion of fat, and prevent and treat obesity and lipid-related metabolic diseases.

In one specific embodiment, the adipocyte differentiation inhibition and triglyceride inhibition effects of dihydro-atermic acid were examined using adipocyte (3T3-L1). As a result, as the concentration of dihydro-atermic acid increased, The amount of fat accumulation and triglyceride was decreased, and the weight of the dihydroatomic acid-administered mice tended to decrease. Further, as a result of cellulite improving effect test using a cream containing dihydroartemic acid, the thickness of the dermal subcutaneous tissue interface surface tended to decrease, and skin roughness was also improved.

In another specific embodiment, the skin cumulative stimulation test of the external preparation for skin including dihydroartemic acid showed that it did not show a clear cumulative irritation pattern like the external preparation for skin not containing dihydroartemic acid, Respectively.

The composition for preventing and treating obesity and / or lipid-related metabolic diseases according to the present invention is characterized in that the dihydroatomic acid or its pharmaceutical, cosmetic or pharmacologically acceptable salt is present in an amount of 0.001 to 10% by weight, In an amount of 0.001 to 5% by weight. If the weight of the dihydroartemic acid or its pharmaceutical, cosmetic or pharmacologically acceptable salt is less than 0.001% by weight, the effect of the anti-obesity activity and anti-fat activity is too weak, and if it exceeds 10% by weight, There is a problem that the increase in the effect of atemic acid or its pharmacological, cosmetic or pharmacologically acceptable salts is insignificant and the stability of the form is not ensured.

On the other hand, the composition of the present invention can be used as a pharmaceutical composition for the prevention and treatment of obesity and / or lipid-related metabolic diseases.

The pharmaceutical composition may contain, in addition to the composition for preventing and treating obesity and / or lipid-related metabolic diseases of the present invention, a pharmaceutically acceptable carrier, excipient and diluent. 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 lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, But are not limited to, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrups, methylcellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. It is not. 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 may be administered to mammals such as rats, mice, livestock, humans, and the like by various routes such as parenteral, oral, and the like, and all manner of administration may be expected, for example, oral, rectal or intravenous , Muscle, subcutaneous, intrauterine or intracerebroventricular injection.

The pharmaceutical composition is administered in a pharmaceutically effective amount. In the present invention, a pharmaceutically effective amount means an amount sufficient to treat or prevent a disease at a reasonable benefit / risk ratio applicable to medical treatment or prevention. The effective dose level will depend on the type of disease and its severity, Including the age, weight, health and sex of the patient, sensitivity of the patient to the drug, time of administration of the particular extract used, route of administration and rate of release, duration of treatment, Can be determined according to factors well known in the art. Generally, a dose of 0.1 to 100 mg / kg per day to an adult can be administered once to several times a day. In the case of the external preparation, it is preferable that the dosage is applied to the adult 1 to 5 times a day at a dose of 1.0 to 3.0 ml per day and continued for 1 month or more.

The pharmaceutical composition may be prepared in the form of a unit dose by formulating it with a pharmaceutically acceptable carrier and / or excipient according to a method which can be easily carried out by those having ordinary skill in the art to which the present invention belongs. Into a multi-dose container. The formulations may be formulated into tablets, capsules, powders, granules, suspensions, emulsions, syrups, emulsions, alerts, ointments, sprayers, oils A tablet, a tincture, a bath, a liniment, a lotion, a patch, a pad, a cream, and the like. In addition, it can be preferably used as an external preparation for skin intended for topical administration for application directly to the affected area. In this case, a form such as an ointment, a lotion, a spray or a gel is preferable. These external preparations for skin may also be included in a support base or matrix or the like, which can be applied directly to the treatment site, and examples of the support substrate include gauze or bandages.

 The composition of the present invention can be used as a cosmetic composition for prevention and treatment of obesity and lipid-related metabolic diseases.

The cosmetic composition includes components commonly used in cosmetic compositions in addition to the composition for preventing and treating obesity and lipid-related metabolic diseases of the present invention. Such as antioxidants, stabilizers, solubilizers, vitamins, customary adjuvants such as pigments and flavoring agents, and carriers.

The cosmetic composition may be in the form of a solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant-containing cleansing oil, powder foundation, emulsion foundation, wax foundation, spray, Lotion, essence, nutritional gel or massage cream, but is not limited thereto.

When the formulation of the cosmetic composition is a paste, a cream or a gel, an animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide .

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 formulation of the cosmetic composition is a solution or an emulsion, a solvent, a solubilizing agent or an emulsifying agent may 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 esters of sorbitan, and the like.

When the formulation of the cosmetic composition is a suspension, a carrier such as water, a liquid diluent such as ethanol or propylene glycol, a suspension such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, Crystalline cellulose, aluminum metahydroxide, bentonite, agar or tracant, etc. may be used.

When the formulation of the cosmetic composition is a surfactant-containing cleansing, the carrier component may include aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyltaurate, sarcosinate, fatty acid amide Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives or ethoxylated glycerol fatty acid esters.

The dose of the formulation varies depending on the age, sex, weight, symptom, and administration method of the subject. In the case of the external preparation, it is applied to the adult 1 to 5 times a day in a dose of 1.0 to 3.0 ml per day It is good to do.

 The composition of the present invention can be used as a functional food composition for prevention and improvement of obesity and / or lipid-related metabolic diseases.

The functional food composition may include a food-acceptable food-aid additive in addition to the composition for preventing and treating obesity and / or lipid-related metabolic diseases of the present invention. The food-aid additive contained in the functional food composition of the present invention may be used as a nutrient, a vitamin, an electrolyte, a flavoring agent, a colorant, a protective colloid thickener, a pH adjusting agent, a stabilizer, a preservative, a glycerin, And the like. In addition, the food of the present invention may contain flesh for the production of natural fruit juice, fruit juice drink and vegetable drink. These components may be used independently or in combination.

The functional food may be in the form of a capsule, a tablet, a powder, a granule, a liquid, a ring, a flake, a paste, a syrup, a gel, a jelly and a bar, but is not limited thereto.

The kind of the food is not particularly limited. Examples include dairy products including meats, sausages, breads, chocolates, candies, snacks, confectionery, pizza, ramen noodles, other noodles, gums and ice cream, soups, beverages, tea, drinks, alcoholic beverages and vitamins , And functional foods in a conventional sense.

The composition comprising the dihydroartemic acid of the present invention or a pharmaceutical, cosmetic or pharmacologically acceptable salt thereof as an active ingredient reduces the amount of fat in the body, decreases the content of triglycerides, And prevents digestion. In addition, there is an efficacy of reducing the cellulite layer to prevent and treat obesity and / or lipid-related metabolic diseases. In addition, since the skin has already been proved to be safe in the cumulative stimulation test, it can be safely used even in long-term use, so that it can be safely applied to medicines, cosmetics and functional foods as described above.

According to the present invention, the dihydroatomic acid or its pharmaceutical, cosmetic or pharmacologically acceptable salt can be used for preventing and treating obesity and / or lipid-related metabolic diseases through inhibition of adipocyte differentiation, . Accordingly, a composition comprising dihydroartemic acid or its pharmaceutical, cosmetic or pharmacologically acceptable salt as an active ingredient can be usefully used in medicines, cosmetics and functional foods.

FIG. 1 shows the result of observing the inhibition effect of 3H-3 L1 preadipocyte differentiation by dihydroatomic acid on oil-red O staining.
FIG. 2 shows the results of observing the inhibition effect of 3H-3 L1 preadipocyte differentiation by dihydroatomic acid on Oil-red O staining.
FIG. 3 shows the results of measuring the inhibitory effect on the accumulation of tri-glyceride in 3T3-L1 adipocyte precursor cells by dihydroatomic acid.
FIG. 4 shows the result of measuring the cellulite reducing effect of the dermal subcutaneous tissue interface by dihydroatomic acid. FIG.
5 shows the results of measuring the roughness-improving effect of the surface of the dermis by dihydroatomic acid.

The present invention will be explained in more detail through the following examples. It is to be understood that these embodiments are provided by way of illustration only, and are not intended to limit the scope of the invention.

Example 1. Inhibitory effect of dihydroartemic acid on adipocyte differentiation

(3T3-L1) was purchased from ATCC (American Tissue Culture Collection, USA) in order to examine the effect of dihydroartemisinic acid (DAA, Xi'an Tian Ben Bio-Engineering) And cultured in DMEM medium supplemented with 10% fetal bovine serum (FBS). To differentiate into adipocytes, cells were seeded on a 12-well microplate at a rate of about 90%, and then cultured for another 2 days. MDI (0.5 mM of isobutylmethylxanthin, 1 μM of dexamethasone, 1 μg / mL of insulin) was treated with a cocktail Respectively. After 3 days, the medium was replaced with medium containing insulin (insulin 1 μg / mL), and after 3 days, it was replaced with DMEM medium supplemented with 10% FBS. The MDI cocktail was treated with 10, 25, and 50 μM of dihydroatheximinic acid from the point of induction of differentiation, and then reprocessed at the same concentration every time the culture medium was changed. The amount of fat accumulated in the differentiated cells was stained with Oil RedO staining method, dissolved in isopropyl alcohol, and then measured for optical density at 540 nm. The results are shown in Fig. 1 and Fig.

As a result of experiments, it was confirmed that MDI treatment of immature adipocyte 3T3-L1 induces differentiation into adipocytes and accumulation of intracellular lipids. The result of measurement of absorbance by dyeing with oil red O-1 showed that the concentration of dihydroatomic acid And the inhibition of adipocyte differentiation was observed.

Example 2 Inhibitory Effect of Dihydroartemic Acid on Neutral Fatty Triglycerides

As in Example 1, the immature fat cells 3T3-L1 were treated with MDI to induce differentiation into adipocytes. Then, 10, 25, 50 μM dihydroatomic acid was treated and cultured for 72 hours. The resulting triglyceride was then measured using a triglyceride determination kit (Sigma, USA). The results are shown in Fig.

As a result of the experiment, it was observed that the production of triglyceride, which is a triglyceride, was inhibited as the concentration of dihydroartemic acid increased.

Example 3: Obesity prevention and inhibitory effect by oral administration

To measure the effect of dihydroartemic acid on obesity, ICR male mice (Charles River, Japan) at 6-7 weeks of age were preliminarily raised for 1 week and used in the experiment as 7 mice per group. The animals were housed in a thermostatic chamber set at a temperature of 23 ± 1 ° C, a humidity of 55 ± 5% and an illumination time of 12 hours / day, and Labo MR (manufactured by Nihon Agric. Respectively. Dihydroartemic acid was prepared with liposomal formulation (dissolved in 5% lecithin) to 0.1% and 1%. The concentration of each sample solution was adjusted to be 0.1 ml per 10 g of mouse, and the dose was adjusted to 1.5 g / kg and 1 g / kg. In the normal group, 5% lecithin emulsion was orally administered. The mice were fasted from the day prior to administration and were forced to the next day. The test period was 2 weeks and body weight and general symptoms were measured and observed.

Days Weight (g) Normal group Dihydroartemic acid (0.1%) Dihydroartemic acid (1%) 5 24.5 23.9 24.2 10 30.4 28.8 28.1 15 36.3 33.2 32.3

As shown in Table 1, mice in the group administered with dihydroartemic acid showed a decrease in body weight, and it was observed that the effect was increased as the administration concentration was increased.

Example 4: Improvement of cellulite activity of dihydroartemic acid

4-1. Manufacture of creams containing dihydroartemic acid

To confirm the improvement effect of dihydroatomic acid on cellulite, a cream was prepared according to the composition shown in Table 2 below. First, glycerin and butylene glycol were mixed and dissolved at 70 DEG C (water phase part), and the other components except for trimethanol amine were dissolved at 70 DEG C (oil phase part). The oil part was added to the water-based part, and the mixture was firstly emulsified by stirring with a homomixer (Tokushu Kika, Japan), and trimethanolamine was finally added thereto. After the bubbles generated in the mixed solution were removed, the mixture was cooled to room temperature to prepare a cream.

ingredient Content (% by weight) Dihydroartemic acid 0.05 Jojoba oil 5.0 Liquid paraffin 7.0 Cetylaryl alcohol 2.0 Polyglyceryl-3 methylglucose distearate 2.0 Glyceryl stearate 0.5 Squalane 3.0 Propylene glycol 4.0 glycerin 5.0 Triethanolamine 0.3 Carboxyvinyl polymer 0.3 Tocopheryl acetate 0.2 Preservative, incense a very small amount Purified water Balance Sum 100

4-2. Cellulite improvement test

Using the cream prepared in Example 4-1, 20 adults were applied around the thighs twice a day, morning and evening for 4 weeks, and the dermal subcutaneous tissue interface thickness and skin roughness were measured. The dermal subcutaneous tissue interface thickness was analyzed by ultrasonic imaging of the skin layer using Dermascan ^® C (Cortex, Denmark) and then analyzed using B - scan mode adapted to the dermal subepithelial interface thickness measurement. Skin roughness was measured using PRIMOS ^® Lite (GFM, Germany). 3D measurement results of PRIMOS Lite ^® were analyzed by the parallel projection stripes projected onto the skin using the changed degree PRIMOS Lite ^® analysis software by the skin surface height. As a result, as shown in FIGS. 4 and 5, cellulite was decomposed due to a decrease in the thickness of the dermal subcutaneous tissue interface with cream containing dihydroartemic acid, and the value of the skin height parameter was small, Improved.

Example 5: Safety test of dihydro atermic acid on human skin

5-1. Preparation of external skin preparation containing dihydroartemic acid

In order to confirm that dihydroartemic acid was safe for human skin, a skin external preparation containing dihydroartemic acid was prepared by the ingredients and contents shown in Table 3 below, and skin safety verification test was conducted. 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 trimethanol amine were dissolved at 70 캜 (oil part). The oil part was added to the water-based part, and the mixture was firstly emulsified by stirring with a homomixer (Tokushu Kika, Japan), and trimethanolamine was finally added thereto. After the bubbles generated in the mixed solution were removed, the mixture was cooled to room temperature to prepare an external preparation for skin.

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

5-2. Skin Cumulative Stimulation Test

Using the skin external preparation prepared in Example 5-1, a total of 9 times 24 hour accumulation pellets were performed on the upper forearm every 30 days in healthy adults to determine whether dihydroartemic acid stimulates the skin Respectively. As a control group, a skin external preparation containing no dihydroartemic acid as a squalane base was used.

The pilling method was carried out using a Finn chamber (Epitest Ltd, Finland), and 15 l of the external preparation for skin was dripped into the chamber, followed by applying a patch. The degree of the skin reaction on each occasion was scored using Equation 1, and the results are shown in Table 3 below.

[Experimental Equation 1]

Average response rate = {[Response index × response / total number of subjects × maximum score (4 points)] × 100} / number of tests

At this time, ±, 1, 2, and ++ were given a score of ±, 1, and 4, respectively, and a safe composition was determined when the average degree of reaction was less than 3.

In Table 4, in the test group, the number of persons corresponding to ±, +, and ++ was 1 in 1st week, 1 in 2nd, 0 in 0, and no reaction occurred after that. As a result of calculation according to the above formula, the average reactivity of the control group was 0.00 and the average reactivity of the test group was 0.13 to 3 or less.

Production Example 1: Preparation of cosmetic material

1-1. Production of flexible lotion

As shown in the following Table 5, a lotion lotion containing dihydroartemic acid as an active ingredient was prepared by a conventional method.

ingredient Content (% by weight) 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 6 below, a nutritional lotion containing dihydroartemic acid as an active ingredient was prepared according to a conventional method.

ingredient Content (% by weight) 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 dihydroartemic acid as an active ingredient was prepared according to a conventional method as shown in Table 7 below.

ingredient Content (% by weight) 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 dihydroartemic acid as an active ingredient was prepared according to a conventional method as shown in Table 8 below.

ingredient Content (% by weight) 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

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

ingredient Content (% by weight) 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 dihydroartemic acid as an active ingredient, the ingredients shown in Table 10 below were mixed and filled in airtight bags to prepare powders.

ingredient Content (g) Dihydroartemic acid 2 Lactose One

2-2. Manufacture of tablets

In order to prepare tablets containing dihydroartemic acid as an active ingredient, tablets were prepared by mixing the ingredients shown in the following Table 11 and then tableting according to a conventional method for producing tablets.

ingredient Content (mg) Dihydroartemic acid 100 Corn starch 100 Lactose 100 Magnesium stearate 2

2-3. Preparation of capsules

In order to prepare a capsule containing dihydroartemic acid as an active ingredient, the following ingredients in Table 12 were mixed and filled in gelatin capsules according to the conventional preparation method of capsules to prepare capsules.

ingredient Content (mg) Dihydroartemic acid 100 Corn starch 100 Lactose 100 Magnesium stearate 2

Claims (7)

Prevention of lipid-related metabolic diseases selected from obesity comprising dihydroartemisinic acid or a pharmaceutically acceptable salt thereof as an active ingredient, or at least one selected from diabetes, hypertension, stroke, hyperlipidemia, arteriosclerosis or cardiovascular disease And pharmaceutical compositions for therapeutic use.
2. The pharmaceutical composition according to claim 1, wherein the dihydroatomic acid or pharmaceutically acceptable salt thereof is contained in an amount of 0.001 to 10% by weight based on the total weight of the total composition.
delete A cosmetic composition for preventing and improving obesity comprising dihydroartemisinic acid or a cosmetically acceptable salt thereof as an active ingredient.
5. The cosmetic composition according to claim 4, wherein the dihydroatomic acid or cosmetically acceptable salt is contained in an amount of 0.001 to 10% by weight based on the total weight of the total composition.
Related diabetes, hypertension, stroke, hyperlipidemia, atherosclerosis, or cardiovascular disease, which comprises dihydroartemisinic acid or a pharmaceutically acceptable salt thereof as an active ingredient. And functional food composition for improvement. delete

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