KR20150087715A - Composition containing Artemisia annua extract, and artemisinin or dihydroartemisinin from Artemisia annua extract for preventing or treating liver cancer - Google Patents

Abstract

The present invention relates to a composition which contains a mugwort (Artemisia annua) extract as an active ingredient and used for the prevention and treatment of the liver cancer. More specifically, the composition includes artemisinin or dihydroartemisinin in the mugwort extract. The mugwort extract, artemisinin, or dihydroartemisinin can significantly alleviate the liver cancer to be utilized for the prevention and treatment of the liver cancer.

Description

(Artemisia annuum extract or Artemisia annua extract for treating or treating liver cancer comprising Artemisinin or dihydroartemisinin), a composition for preventing or treating liver cancer,

The present invention relates to a composition for preventing or treating liver cancer including Artemisia sp. Extract, atemicinin or dihydroartemisinin.

Liver cancer is one of the most deadly cancers in the world, and it has become a serious problem especially in the Asian countries including Korea. Solid tumors account for more than 90% of hepatocellular carcinoma are difficult to treat and their prognosis is very poor. The reason for this is that most of the cases are not asymptomatic at the beginning, Because it often starts from cirrhosis and is likely to die from its complications. The most important method for the treatment of these cancers is surgical removal. Liver transplantation, hepatic artery embolization, percutaneous ethanol injection, and immunochemotherapy are used when surgery can not remove cancerous tissue. Hepatectomy is a relatively early treatment for patients with no metastasis. Currently, about 20% of patients with hepatocellular carcinoma undergo hepatic resection. However, long-term survival rates for patients with hepatocellular carcinoma are high It is not. Especially, there are many patients who have survival rate of 30-40% within 5 years after surgery. In addition, surgical treatment may cause side effects such as bleeding and infection, and may cause hypersensitivity reactions, chills and fever, nausea and vomiting, general weakness, anorexia, headache, anemia, leukopenia, etc. Can occur.

Therefore, many studies have been conducted to find natural products showing anticancer effect against liver cancer with less toxicity and side effects. In particular, studies on the development of anticancer drugs and anticancer drugs using relatively safe human medicines have been actively conducted .

On the other hand, artemisia annua is a perennial plant belonging to Asteraceae family, which is distributed in Korea, Japan, Taiwan, Mongolia and Siberia. It is a plant which grows in a gardens, a pit and a river, and is about 1m in height. It has no hair on the whole grass and has an unusual smell. It is used for treatment of fever, schizophrenia, digestion and dyspepsia. , Spices, and vinegar.

Artemisinin, arteannuin B, artemisininic acid, dihydroartmisinic acid, and the like are included in the artemisia annua, Alpha-epoxydihydroartemisinic acid, Arteannuin L, Arteannuin N, Dihydroarteannuin B, 3, < RTI ID = 0.0 & 3 ', 7-trimethylquercetin, 3,4', 7-trimethylquercetin.

The inventors of the present invention have conducted studies on natural products and compounds separated therefrom in order to develop drugs having excellent effects for preventing or treating liver cancer. .

It is an object of the present invention to provide a composition for preventing or treating liver cancer including Artichoke extract, atemicinin or dihydroartemisinin.

In order to accomplish the above object, the present invention provides a pharmaceutical composition for preventing or treating liver cancer including Artichoke extract, atemicinin or dihydroartemisinin.

In addition, the present invention provides a food composition for preventing or ameliorating liver cancer including Artichoke extract, atemicinin or dihydroartemisinin.

The artichoke extract of the present invention, atemicinin or dihydroatomicinin is excellent in improving liver cancer, and thus can be effectively used for preventing or treating liver cancer.

FIG. 1 is a graph showing the results of measurement of the inhibitory effect of atemicinin and dihydroatomicinin on the growth of liver cancer cells.

The present invention provides a composition for preventing or treating hepatocellular carcinoma, which contains an extract of Artemisia princeps as an active ingredient.

The present invention also provides a composition for preventing or treating liver cancer comprising atemicinin or dihydroatomicinin as an active ingredient.

The composition comprises a pharmaceutical composition and a food composition.

Hereinafter, the present invention will be described in detail.

The ragweed extract, which is an active ingredient of the present invention, can be obtained by a conventional extraction method.

In the present invention, it was obtained by the following method.

First, the mugwort is washed cleanly with water to remove foreign matter, and then dried and pulverized at room temperature. The ground mite powder is immersed in a solvent and extracted overnight. The extraction solvent is not limited thereto, but at least one solvent selected from water, an alcohol having 1 to 4 carbon atoms, and a mixed solvent thereof may be used, and ethanol is preferable. The crude extract is filtered, and then the solvent is evaporated and concentrated to give the final crude extract.

In addition, the active ingredients of the present invention, atemicinin and dihydroatomicinin, can be obtained by conventional extraction and fractionation methods, or they can be synthesized by an organic synthesis method or purchased commercially available reagents.

A typical extraction method is as follows.

The rabbit extract is filtered and concentrated to obtain crude extract. The obtained crude extract is suspended in distilled water and fractionated with hexane, chloroform, ethyl acetate and n-butanol in order. These fractions are chromatographed to give atemicinine and dihydroatomicinin.

Artemisinin or dihydroartemisinin of the present invention is excellent in improving liver cancer, and thus can be effectively used for prevention or treatment of liver cancer.

The liver cancer may be liver cancer derived from hepatitis B virus.

The composition of the present invention may further contain one or more known active ingredients having an effect of preventing or treating liver cancer together with Artemisinin extract or Artemisinin or Dihydroartemisinin.

The compositions of the present invention may further comprise suitable carriers, excipients and diluents conventionally used in the manufacture of pharmaceutical compositions. In addition, it can be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, oral formulations such as syrups and aerosols, external preparations, suppositories and sterilized injection solutions according to a conventional method. Suitable formulations known in the art are preferably those as disclosed in Remington ' s Pharmaceutical Science, recently, Mack Publishing Company, Easton PA. Examples of carriers, excipients and diluents which may be included include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, Cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil. When the composition is formulated, it is prepared using a diluent such as a filler, an extender, a binder, a wetting agent, a disintegrant, a surfactant, or an excipient usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, sucrose, lactose, Gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Examples of the liquid preparation for oral administration include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included . Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.

The term "administering" as used herein is meant to provide any desired composition of the invention to a subject in any suitable manner.

The preferred dosage of the pharmaceutical composition of the present invention varies depending on the condition and the weight of the individual, the degree of disease, the type of drug, the route of administration and the period of time, but can be appropriately selected by those skilled in the art. For the desired effect, the rabbit extract of the present invention may be administered in an amount of 1 mg / kg to 10000 mg / kg per day, and may be administered once a day or divided into several times.

The pharmaceutical composition of the present invention may be administered to a subject in various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine dural or intracerebral injection.

The composition of the present invention can be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy and biological response modifiers for the prevention and treatment of liver cancer.

In the present invention, the term "health functional food" refers to a food having a biological control function such as prevention and improvement of disease, bio-defense, immunity, recovery after disease and aging inhibition.

The composition of the present invention may be added to a health functional food for the purpose of preventing or improving liver cancer. When the rabbit extract of the present invention is used as a food additive, the ragweed extract can be used as it is or can be used together with other food or food ingredients, and can be suitably used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to the intended use (prevention, health or therapeutic treatment). Generally, the ragweed extract of the present invention is added in an amount of not more than 15% by weight, preferably not more than 10% by weight based on the raw material, when the food or beverage is produced. However, in the case of long-term intake for the purpose of health and hygiene or for the purpose of controlling health, the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount exceeding the above range.

There is no particular limitation on the kind of the food. Examples of foods to which the above substances can be added include dairy products including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen and other noodles, gums, ice cream, various soups, drinks, tea, Alcoholic beverages, and vitamin complexes, all of which include health foods in a conventional sense.

The health beverage composition of the present invention may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary beverages. The natural carbohydrates may be monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, natural sweeteners such as dextrin and cyclodextrin, synthetic sweeteners such as saccharine and aspartame, and the like. The ratio of the natural carbohydrate is generally about 0.01 to 10 g, preferably about 0.01 to 0.1 g per 100 ml of the composition of the present invention.

In addition to the above, the composition of the present invention may further contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, A carbonating agent used in a carbonated beverage, and the like. In addition, the composition of the present invention may comprise flesh for the production of natural fruit juices, fruit juice drinks and vegetable drinks. These components may be used independently or in combination. Although the ratio of such additives is not critical, it is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.

Hereinafter, preferred examples, experimental examples, and formulation examples are provided to facilitate understanding of the present invention. However, the following examples, experimental examples and preparation examples are provided only for the purpose of easier understanding of the present invention, and the present invention is not limited thereto.

EXAMPLES Example 1 Preparation of Dogwood Mugwort Extract

The dogs were washed with water to remove impurities, and then dried and pulverized at room temperature. The powdered ground mite powder was immersed in ethanol and extracted overnight. After filtering the above artichoke extract, the solvent was evaporated and concentrated to give the final artichoke extract.

Example 2. Obtaining atemicinin and dihydroatomicinin

2-1. Isolation of Atemicinin and Dihydro Atemicinin from Artemisia princeps

The rabbit extract prepared in Example 1 was filtered and concentrated to obtain crude extract. The obtained crude extract was suspended in distilled water and fractionated successively with hexane, chloroform, ethyl acetate and n-butanol. These fractions were chromatographed to give atemicinine and dihydroatomicinin.

2-2. Purchase of Atemicinin and Dihydro Atemicinin

Atemicinin and dihydroatomicinin were purchased from Sigma-Aldrich by purchasing pure substances.

Experimental Example 1. Confirmation of the inhibitory effect of atemicinin and dihydroatomicinin on the growth of liver cancer cells

In order to confirm the inhibitory effect of atemicinin and dihydro - atemicinin, which are the indicators of the extract of Artemisia princeps, on the growth of liver cancer cells, cytotoxicity by MTT was measured. 5x10 < ³ > mouse liver cancer cell lines hepa1c1c7 and BpRc1 and human hepatocarcinoma cell line HepG2 cells were dispensed into 96-well plates. After 24 hours, the samples were diluted by concentration and treated with cells. After the sample was treated, MTT solution of 1 mg / mL (final concentration) was treated and dissolved in 150 μL of DMSO for 2 hours. The absorbance at 570 nm was measured and the following equation was calculated. The results are shown in FIG.

Cell viability (%) = Abs _sample / Abs _solvent × 100

As shown in FIG. 1, atemicinin did not inhibit cell growth in hepa1c1c7, BpRc1 and HepG2 when treated for 24 hours, but dihydroatomicinin showed cell growth inhibition effect. As the treatment for 48 hours and 72 hours was prolonged, the effect of atemicinin and dihydroatomicinin on cell growth was increased and dihydroatomicinin was more sensitive. In addition, both substances were found to be more sensitive to mouse liver cancer cell line than human liver cancer cell line.

Hereinafter, the pharmaceutical composition of the present invention and the pharmaceutical composition of the food composition will be described, but the present invention is not intended to be limited thereto but is specifically described.

Formulation Example 1. Preparation of pharmaceutical preparations

1. Manufacturing of powder

Artichoke extract, atemicinin or dihydroartemisinin 20 mg

Lactose 100 mg

Talc 10 mg

The above components are mixed and filled in airtight bags to prepare powders.

2. Preparation of tablets

10 mg of Artemisinin or dihydroartemisinin

Corn starch 100 mg

Lactose 100 mg

Magnesium stearate 2 mg

After mixing the above components, tablets are prepared by tableting according to the usual preparation method of tablets.

3. Preparation of capsules

10 mg of Artemisinin or dihydroartemisinin

Crystalline cellulose 3 mg

Lactose 14.8 mg

Magnesium stearate 0.2 mg

The above components are mixed according to a conventional capsule preparation method and filled in gelatin capsules to prepare capsules.

4. Preparation of injections

10 mg of Artemisinin or dihydroartemisinin

180 mg mannitol

Sterile sterilized water for injection 2974 mg

Na ₂ HPO ₄ 2H ₂ O 26 mg

(2 ml) per 1 ampoule in accordance with the usual injection preparation method.

5. Manufacture of liquids

Artichoke extract, atemicinin or dihydroartemisinin 20 mg

10 g per isomer

5 g mannitol

Purified water quantity

Each component was added and dissolved in purified water according to the usual liquid preparation method, and the lemon flavor was added in an appropriate amount. Then, the above components were mixed, and purified water was added thereto. The whole was added with purified water to adjust the total volume to 100 ml, And sterilized to prepare a liquid preparation.

[Formulation example 2. Preparation of food preparation]

1. Manufacture of health food

Artemisinin, or dihydroartemisinin 100 mg

Vitamin mixture quantity

70 g of vitamin A acetate

Vitamin E 1.0 mg

Vitamin B1 0.13 mg

0.15 mg of vitamin B2

Vitamin B6 0.5 mg

0.2 g of vitamin B12

Vitamin C 10 mg

Biotin 10 g

Nicotinic acid amide 1.7 mg

Folate 50 g

Calcium pantothenate 0.5 mg

Mineral mixture quantity

1.75 mg of ferrous sulfate

0.82 mg of zinc oxide

Magnesium carbonate 25.3 mg

Potassium monophosphate 15 mg

Secondary calcium phosphate 55 mg

Potassium citrate 90 mg

Calcium carbonate 100 mg

Magnesium chloride 24.8 mg

Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a composition suitable for health food as a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional method for producing healthy foods , Granules can be prepared and used in the manufacture of health food compositions according to conventional methods.

2. Manufacture of health drinks

Artemisinin, or dihydroartemisinin 100 mg

Vitamin C 15 g

Vitamin E (powder) 100 g

19.75 g of ferrous lactate

3.5 g of zinc oxide

Nicotinic acid amide 3.5 g

Vitamin A 0.2 g

Vitamin B1 0.25 g

Vitamin B2 0.3g

Water quantification

The above components were mixed according to a conventional health drink manufacturing method, and the mixture was stirred and heated at 85 DEG C for about 1 hour. The solution thus prepared was filtered and sterilized in a sterilized 2 liter container, It is used in the production of the health beverage composition of the invention.

Although the compositional ratio is relatively mixed with a component suitable for a favorite drink, it is also possible to arbitrarily modify the compounding ratio according to the regional or national preference such as the demand class, the demanding country, and the use purpose.

Claims (8)

TECHNICAL FIELD The present invention relates to a pharmaceutical composition for preventing or treating liver cancer, which comprises an extract of Artemisia princeps as an active ingredient. The pharmaceutical composition for preventing or treating liver cancer according to claim 1, wherein the rabbit extract is extracted with at least one solvent selected from the group consisting of water, an alcohol having 1 to 4 carbon atoms, and a mixed solvent thereof. The pharmaceutical composition for preventing or treating liver cancer according to claim 1, wherein the liver cancer is hepatitis B virus-derived liver cancer. A pharmaceutical composition for the prophylaxis or treatment of liver cancer, which comprises artemisinin or dihydroartemisinin as an active ingredient. [Claim 5] The pharmaceutical composition according to claim 4, wherein the atemicinin or dihydroatomicinin is isolated from a ragweed extract. A food composition for prevention or amelioration of liver cancer, comprising an extract of Artemisia princeps as an active ingredient. A food composition for preventing or ameliorating liver cancer, which comprises as an active ingredient artemisinin or dihydroartemisinin. 8. The food composition according to claim 7, wherein the atemicinin or dihydroatomicinin is isolated from a ragweed extract.

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