KR100247568B1 - Atherosclerosis pharmaceutical composition - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for inhibiting atherosclerosis, and more particularly, the extract extracted from the leaves and stems of Korean mistletoe (Viscum album var. Coloratum) is contained as an active ingredient, which is particularly effective in preventing and treating atherosclerosis. It relates to a high atherosclerosis pharmaceutical composition.

Description

Atherosclerosis pharmaceutical composition

The present invention relates to a pharmaceutical composition for inhibiting atherosclerosis, and more particularly, the extract extracted from the leaves and stems of Korean mistletoe (Viscum album var. Coloratum) is contained as an active ingredient, which is particularly effective in preventing and treating atherosclerosis. It relates to a high atherosclerosis pharmaceutical composition.

"Arteriosclerosis" is a lesion that causes fat, mainly cholesterol and triglycerides, to deposit in the blood vessels, narrowing the lumen of the vessels and losing elasticity. There are various causes such as abnormal lipid metabolism, abnormal hormone metabolism, genetic predisposition, and dietary life, but one of them is not the cause but several causes are overlapping each other.

Lesions can occur throughout the body, but are a clinical problem when they appear in blood vessels such as the aorta, brain, cardiovascular artery, and kidneys. For example, aneurysms in the aorta, cerebral thrombosis, cerebral atherosclerosis, and cerebral hemorrhage in the brain, angina and myocardial infarction in the heart, and neurosis and hypertension in the kidneys are the main causes of atherosclerosis. There are three types of atherosclerosis: atherosclerosis, medial calcification (Monckeberg), and arteriolosclerosis. In particular, hyperlipidemia, hypertension, smoking and diabetes are known as the major causes of atherosclerosis, and high incidence in economically rich countries. In order to prevent and treat such arteriosclerosis, medicines generally limiting animal fats, ingesting sufficient vitamins and proteins, and reducing serum cholesterol are taken.

In addition, in the present invention, the Korean mistletoe extract intended to be included as an active ingredient of the pharmaceutical composition for treating atherosclerosis has not been used for the purpose of treating such atherosclerosis.

Mistletoe (Loranthaceae) is an evergreen shrub, a parasitic plant that lives on other trees. In folk medicine, mistletoe leaves and stems are known to be effective in preventing hypertension, analgesia, back pain, frostbite, and miscarriage, but there are no scientific studies on their efficacy. In folk medicine, mistletoe leaves and stems of mistletoe, and then take a certain amount of water for drinking or making tea in boiling water and drinking it.However, when heated and extracted in this way, the physical and chemical changes of the active ingredients in the extract There is a problem that can be caused.

In addition, it is known that the European mistletoe is used in the European folk medicine for the purpose of treating hypertension.

Recently, lectin-based protein components have been extracted from Korean mistletoe, and its efficacy, particularly antitumor activity, has been reported [T.A. Khwaja, Experientia, 36, 599, 1986 & U.S. Pat. J.B. Kim, Kor. J. Pharmacogn. 25 (2), 132, 1994 & Korean Patent Publication No. 94-3561; W.B. Park, Yakhak Hoeji, 39 (1), 24, 1995]. However, it is not known that Korean mistletoe extract is effective in inhibiting arteriosclerosis.

In the present invention, it was found that the extract of Korean mistletoe (Viscum album var. Coloratum) is effective in the prevention and treatment of atherosclerosis, by extracting the active ingredient from the leaves or stems of Korean mistletoe (Viscum album var. Coloratum) by solvent extraction The purpose of the present invention is to provide an effective pharmaceutical composition for the prevention and treatment of atherosclerosis obtained by obtaining an extract without any physical and chemical changes as an active ingredient.

The present invention is characterized by a pharmaceutical composition for inhibiting arteriosclerosis, which contains an extract from the leaves or stems of Korean mistletoe (Viscum album var. Coloratum) as an active ingredient.

Referring to the present invention in more detail as follows.

Korean mistletoe (Viscum album var. Coloratum) used in the present invention is a parasitic plant that is wild throughout the country in Korea, in the branches of various types of host plants such as oak, chestnut, teal, hackberry, birch, pine, bark, apple, etc. It is an evergreen shrub that grows.

In the present invention, a polar solvent such as water or lower alcohol is used as an extraction solvent for extracting the active ingredient from the leaves and stems of Korean mistletoe (Viscum album var. Coloratum). However, while the conventional extraction method using a solvent is carried out under warming, there is a problem that physical and chemical changes of the active ingredients occur, whereas in the present invention, by extracting within the range of 0 ℃ ~ 40 ℃ Physical and chemical changes were suppressed. Then, the extract is concentrated using reduced pressure concentration or freeze-drying, and then prepared in extract or powder form containing a certain ratio of solvent. In addition, extracts or powdered Korean mistletoe extract as an active ingredient is formulated with conventional excipients used in pharmaceutical fields such as starch, purified water, and the like, and formulated into tablets, capsules, pills, granules, liquids, and the like.

Therefore, the present invention includes a pharmaceutical composition containing the Korean mistletoe extract as an active ingredient, the Korean mistletoe extract as an active ingredient has a superior atherosclerotic inhibitory activity that is contained within the range of 0.5 to 50% by weight in the total pharmaceutical composition. Indicates. The dosage of these drugs varies slightly depending on the age of the patient or the severity of the disease, but once or twice a day and once or twice a capsule (capsule, bottle).

Although this invention is demonstrated in more detail based on the following Example, this invention is not limited by an Example.

Example 1 Water Extract of Korean Mistletoe Leaf and Stem

After collecting Korean mistletoe (Viscum album var. Coloratum), wash leaves and stems 1-2 years old clean, dry it carefully to avoid browning in a well-ventilated place, and then crush it to 1cm or less and then weigh 1kg. Was taken and used as a sample. Distilled water was added so that the sample was sufficiently submerged, and it was immersed at 4 degreeC for 24 hours or more, and it centrifuged and filtered. The filtrates were repeatedly extracted three times in the same manner and combined and dried by lyophilization. As a result, 241.5 g of a powder was obtained.

Example 2 Methanol Extract of Korean Mistletoe Leaf and Stem

1 kg of the sample treated in the same manner as in Example 1 was taken, and 80% methanol was added thereto to be sufficiently immersed and deposited at 4 ° C. for 7 days, followed by filtration. The extraction was repeated three times in the same manner and the combined filtrates were concentrated under reduced pressure in vacuo to give 287.9 g of powder.

Preparation Example 1 Preparation of Tablet

Mistletoe extract according to the present invention was taken to be 20% of the total content, and then purified by mixing conventional excipients used in the pharmaceutical field.

20 g extract (Example 1)

Lactose 60g

15 g of crystalline cellulose

2g magnesium stearate

Purified water

----------------

100 g

After crushing and mixing the ingredients listed above, tablets were prepared by a direct tableting method. The total amount of each tablet was 100 g, and the content of the active ingredient was 20 g.

Preparation Example 2 Preparation of Capsule

The mistletoe extract according to the present invention was taken to be 20% of the total content, and then uniformly mixed with conventional excipients used in the pharmaceutical field. The mixture was powdered to an appropriate size and then prepared by filling a predetermined amount into hard gelatin capsules for medicine and food.

20 g extract (Example 1)

Corn Starch 60g

Carboxymethylcellulose 15g

2g magnesium stearate

Purified water

----------------

100 g

A powder was prepared by crushing and mixing the ingredients listed above. 300 mg of the powder was put into the hard capsule to prepare a capsule.

Production Example 3 Preparation of Fluid

The mistletoe extract according to the present invention was taken to be 20% of the total content, and then uniformly mixed with conventional excipients used in the pharmaceutical field.

20 g extract (Example 1)

Fructose 4g

0.08 g sodium benzoate

0.01 g of methyl paraoxybenzoate

Paraoxybenzoic acid propyl 0.001g

Purified water

----------------

100 g

Experimental Example 1 Acute Toxicity Test (LD ₅₀ Measurement)

63 mg / kg, 125 mg / kg, 250 mg / kg, 500 mg / kg, Korean mistletoe extract extracted in Example 1 and Example 2, respectively, with 5 to 6 ICR mice of about 20 g body weight Once orally administered at a dose of 1000 mg / kg, 2000 mg / kg, 4000 mg / kg, the number of dead mice and gross abnormalities were observed for 14 days from the day of administration. The results are shown in Table 1 below.

According to the results of Table 1, the Korean mistletoe extract was almost negligible as acute toxicity (LD ₅₀ ) of more than 4g / kg.

Experimental Example 2 Measurement of Atherosclerosis Inhibitory Effect

Eight male rats were used as a group, and only normal olive oil and 40 mg / kg cholesterol and 3200 IU / kg of cholesterol in control group were dissolved in olive oil at the same time and administered orally once a day for 28 days for atherosclerosis. After induction, the mistletoe extracts extracted in Examples 1 and 2 and Comparative Examples 1 and 2 were each post-treated for 7 days at a concentration of 0.250 g / kg. The treatment method was orally administered once a day, and the same amount of normal saline was administered orally to the normal group and the control group.

On the last day of the experiment, normal and control groups were fasted for 12 hours, and blood was collected from the abdominal aorta under urethane anesthesia. The obtained blood was centrifuged at 3000 rpm for 15 minutes to collect unhemolyzed serum, and then, by enzyme method, the total cholesterol content (T. cholesterol) and the content of HDL-cholesterol (HDL-chol / T. Cholesterol) contained in total cholesterol. ) And the serum triglyceride content and calcium content were measured using a kit for measurement, respectively. As a result, it is as showing in following Table 2.

As described above, the extract of the leaves and stems of Korean mistletoe obtained by the present invention was excellent in inhibiting atherosclerosis. In particular, the total cholesterol and triglyceride levels of arteriosclerosis-induced rats were significantly lower than those of normal rats, whereas HDL-cholesterol levels were significantly higher than those of normal rats. have.

Claims (3)

A pharmaceutical composition for inhibiting atherosclerosis, characterized in that the leaf extract, stem extract, or a mixture of leaves and stems of Korean mistletoe (Viscum album var. Coloratum) is contained as an active ingredient. The pharmaceutical composition of claim 1, wherein the extract is contained in an amount of 0.5 to 50% by weight in the pharmaceutical composition. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition is formulated as a tablet, capsule, or fluid.