KR20000051921A - Pharmaceutical compositions - Google Patents

Abstract

PURPOSE: A pharmaceutical composition and a preparation method thereof are provided to inhibit cholesterol and neutral fat from a deposit on a blood vessel and to prevent and treat hypertension by using Korean mistletoe. CONSTITUTION: A pharmaceutical composition comprises a therapeutically effective amount i.e., 0.01-50 wt% of an extract of Korean mistletoe's leaves, stems or roots. The preparation method comprises: defatting the sample using nonpolar solvents to extract from the Korean mistletoe; vacuum concentrating the extracts obtained using water-soluble organic solvent; extracting with low polar organic solvent which dissolves the concentrate in water.

Description

Pharmaceutical composition {PHARMACEUTICAL COMPOSITIONS}

The present invention relates to a pharmaceutical composition containing an extract extracted from the leaves, stems or berries of Korean mistletoe (Viscum album var.coloratum) as an active ingredient, and to a method for preparing the same. The present invention relates to a pharmaceutical composition which inhibits deposition in blood vessels and exhibits an excellent effect on lowering blood pressure, and a method of manufacturing the same.

Due to the richness of today's economy, excessive cholesterol and triglycerides are deposited in blood vessels due to the intake of large amounts of animal fat and lipid metabolism due to changes in diet, and narrowing the lumen of the vessels, causing various types of lesions related to circulatory diseases.

These cholesterol and triglyceride lesions can occur throughout the body and cause cerebral thrombosis, cerebral arteriosclerosis, cerebral hemorrhage, angina pectoris, myocardial infarction, neurosis and hypertension. To prevent and treat such lesions, improve animal-oriented diets characterized by high fat and low fiber, avoid intake of large amounts of cholesterol and triglycerides, and consume enough vitamins and fiber through vegetables, fish and fruits. Some people use drugs that reduce cholesterol.

Korean mistletoe (Viscum album var.coloratum) is an evergreen shrub belonging to the group of the mistletoe family (Loranthaceae) .A parasitic plant that grows on other trees and grows in folk medicine. Although it is known to be effective for drinking adult diseases, there is little pharmaceutical research and drug development using Korean mistletoe.

However, Europe has long been studying European mistletoe, which contains different ingredients from Korean mistletoe. As a result of research, inositol, beta-anoline, rufeol, biscotoxin, biscumin, flavonoids, polysaccharides, lectin-based proteins and polyphenol-based compounds have been identified. It is known to have toxicity. Also, in Germany and Switzerland, anti-cancer adjuvants and drugs related to adult diseases, manufactured using European mistletoe as a main ingredient, have been developed and marketed as tablets, liquids, and the like. Research into the development of anti-tumor and AIDS drugs is very active.

In the present invention, it was found that the extract of Korean mistletoe (Viscum album var.coloratum) inhibits cholesterol and triglycerides and has an excellent effect on lowering blood pressure, and is active from the leaves, stems or berries of Korean mistletoe (Viscum album var.coloratum). The purpose of the present invention is to provide a pharmaceutical composition and a method for producing the same, which extracts a solvent and suppresses the deposition of cholesterol and triglycerides in blood vessels as an active ingredient and shows an excellent effect on the prevention and treatment of hypertension. have.

The present invention inhibits the deposition of cholesterol and triglycerides containing extracts from the leaves, stems, or berries of Korean mistletoe (Viscum album var.coloratum) as active ingredients, and shows a pharmaceutical composition showing an excellent effect on lowering blood pressure and The manufacturing method is characterized.

The present invention will be described in detail as follows.

Korean mistletoe used in the present invention (Viscum album var.coloratum) is an evergreen shrub that grows on branches such as oak, chestnut, fir, pine, and apple trees as wild plants throughout Korea.

In the present invention, a polar solvent such as water and a lower alcohol and a nonpolar solvent such as hexane, ether and chloroform can be used as an extraction solvent for extracting the active ingredient from the leaves, stems or berries of Korean mistletoe (Viscum album var.coloratum). For the extraction method, a general solvent extraction method and an ultrasonic extractor were used.

Solvent extraction method. The leaves and stems of mistletoe are dried and pulverized finely, and then sufficiently degreased at room temperature by adding small or nonpolar solvents such as ethyl acetate, chloroform, dieth ether, and n-hexane, and degreased and filtered. A water-soluble lower alcohol of 5 to 10 times the weight is added to the residue, followed by extraction at room temperature. Alternatively, the sample is extracted with a water-soluble lower alcohol, the extract is concentrated under reduced pressure, and then degreased using a small polar or nonpolar organic solvent. The extract thus obtained is concentrated under reduced pressure, and then methanol extract is obtained by adding methanol to concentrate the extract under reduced pressure to prepare a powder or a solvent containing a fixed ratio.

Extraction method using ultrasonic extractor. The same sample used in the solvent extraction method is taken, placed in an ultrasonic extractor containing a sufficient amount of hexane, extracted at room temperature, degreased, and filtered. A water-soluble lower alcohol having a weight of 5 to 10 times was added to the residue, followed by extraction at room temperature. The filtrate was concentrated under reduced pressure, and methanol extract was added thereto to concentrate under reduced pressure to prepare a powder or extract. Alternatively, the sample is placed in an ultrasonic extractor, extracted with a water-soluble lower alcohol, the extract is concentrated under reduced pressure, degreased using a small polar or nonpolar organic solvent, and concentrated under reduced pressure to prepare a powder or extract. At this time, the ultrasonic frequency is controlled within the range of 10 ~ 50KHz, the extraction method using the ultrasonic extractor saves the extraction time and the extraction efficiency is higher than the solvent extraction method, but there is a disadvantage that the cost for the equipment is added.

Tablets, capsules, pills and tablets are prepared with conventional excipients used in pharmaceutical fields, such as starch and purified water, using methanol extracts of Korean mistletoe (Viscum album var.coloratum) or powdered methanol obtained as above as an active ingredient. Formulate in the form of granules and liquids.

The present invention comprises a pharmaceutical composition containing the extract of Korean mistletoe (Viscum album var.coloratum) as an active ingredient, the extract of Korean mistletoe as an active ingredient is contained within the range of 0.01 to 50% in the total pharmaceutical composition cholesterol and It suppresses triglycerides and shows an excellent blood pressure lowering effect.

The dosage of these drugs varies somewhat depending on the age of the patient or the severity of the disease, but once or twice a day and 1-2 tablets (capsules, bottles) per dose.

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

Example 1 Mistletoe Methanol Extract

The leaves of Korean mistletoe (Viscum album var.coloratum) and 1-2 year old stems were carefully dried to dry and finely pulverized to 1 cm or less and used as samples. 1 kg of the sample was taken and extracted 3 times for 6 days, 3 days and 1 day at room temperature with 5 l of 70% methanol, and the filtrates were combined and concentrated under reduced pressure at 40 ° C. 500 ml of n-hexane was added to the concentrate, shaken well, and the mixture was stirred (repeated until the nucleic acid layer was transparent). The n-nucleic acid layer was removed, and 500 ml of methanol was added to the mixture, followed by stirring. The methanol extracts extracted three times were combined and concentrated under reduced pressure at 40 ° C. to obtain 263.1 g of powder.

Example 2 Mistletoe Water Extract

1 kg of the same sample as in Example 1 was taken, and purified water was added thereto, followed by immersion. The mixture was left overnight at 4 ° C. or lower, and then filtered. The filtrate was repeatedly extracted two times in the same manner and combined and dried by lyophilization to obtain 252.3 g of powder.

Example 3 Mistletoe Methanol Extract Using Ultrasonic Extractor

1 kg of the same sample as in Example 1 was taken into an ultrasonic extractor, and 70% methanol extract extracted three times for 12 hours, 5 hours, and 5 hours at room temperature with 5 liters of 70% methanol was concentrated under reduced pressure at 40 ° C, and then concentrated to n. 500 ml of hexane was added thereto, shaken well, and the mixture was stirred (it was repeated until the nucleic acid layer was transparent). Then, the n-nucleic acid layer was removed, and 500 ml of methanol was added thereto, shaken well, and filtered. The methanol extracts extracted three times were combined and concentrated under reduced pressure at 40 ° C. to obtain 268.3 g of powder. At this time, the frequency of the ultrasonic extractor was adjusted to 25KHz.

However, the yield obtained through the above example was 20-30%, which showed a difference depending on the production of mistletoe.

Example 4: Preparation of Tablets

Methanol extract of Korean mistletoe according to the present invention was taken to be 25% of the total content, and then purified by mixing conventional excipients used in the pharmaceutical field.

After crushing and mixing the ingredients listed above, tablets were prepared. The total amount of each tablet is 100 g.

Example 5 Preparation of Capsules

Methanol extract of Korean mistletoe according to the present invention is taken to be 25% of the total content, and uniformly mixed with conventional excipients used in the pharmaceutical field, and then the granules are granulated to fill a predetermined amount into hard gelatin capsules for medicine and food. Prepared.

After pulverizing and mixing the ingredients listed above to prepare a powder, the capsule was prepared by putting 300mg of powder in a hard capsule.

Example 6 Preparation of Fluid

After the methanol extract according to the present invention is taken to be 0.075% of the total content, and mixed with a conventional excipient used in the pharmaceutical field to be uniform. Each 10 g was charged.

Experimental Example 1 Acute Toxicity Measurement

1) Sample preparation: The water extracts obtained in Examples 1 and 2 were dissolved in water, and methanol extracts were prepared by suspending in saline solution to 0.25g / ml.

2) Experimental method: 10 ICR mice (average body weight 20.0 ± 2.0g) in one group were treated with oral administration of water mist and methanol extract of Korean mistletoe prepared in 1). Observed. As shown in Table 1, the acute toxicity (LD ₅₀ ) for water extracts and methanol extracts of Korean mistletoe is a safe substance with a very low toxicity of more than 4 g / kg.

Experimental Example 2 Measurement of Blood Pressure Inhibitory Effect

1) Sample preparation: Methanol extract of mistletoe obtained in Example 1 was prepared by suspending in saline solution to 0.25g / ml.

2) Experimental Method: Four SHR rats were treated as a group, and the sample prepared in 1) was orally administered once a day for 28 days. Blood pressure was measured 1 hour after drug administration and measured at 7 day intervals. As shown in Table 2, there was no change over time in the control group not administered the mistletoe extract, but the group treated with the methanol extract of mistletoe showed a significant blood pressure-lowering effect.

Experimental Example 3 Measurement of Inhibitory Effect of Cholesterol and Triglyceride

1) Sample preparation: The water extract of the mistletoe and the methanol extract obtained in Example were prepared by suspending in saline solution to 0.25g / ml.

2) Experimental Method: 10 IRC mice were used as a group. In the control group, cholecalciferol and cholesterol were dissolved in olive oil at 3200 IU / kg and 40 mg / kg, respectively, and then orally administered once a day for 28 days. After inducing the lesions, the water extract and methanol extract of Korean mistletoe prepared in 1) were orally administered once a day for 7 days at a concentration of 250 mg / kg, and the normal group was administered only olive oil. In addition, the same amount of saline was administered orally to the control group and the normal group in the same manner. After fasting the control group and the normal group for 12 hours, unbleeded serum was collected by centrifuging blood from the abdominal aorta for 15 minutes under urethane anesthesia, and then contained in total cholesterol content and total cholesterol by enzymatic method. The HDL-cholesterol content (High density 1 ipoprotein) was measured, and triglyceride content and calcium content, which are triglycerides in serum, were measured for each kit. The results are shown in Table 3 below.

As seen above, the solvent extracts of the leaves and stems of Korean mistletoe obtained by the present invention had an excellent blood pressure lowering effect and an excellent inhibitory effect on cholesterol and triglycerides. Methanol extract of Korean mistletoe significantly lowered the blood pressure level of SHR rats, and significantly reduced the total cholesterol level and triglyceride, triglyceride, which induced lesions, while reducing HDL-cholesterol level. It was found that the effect is quite high.

Claims (6)

A pharmaceutical composition for the purpose of preventing and treating hypertension, which contains extracts extracted from each or mixture of leaves, stems and berries of Korean mistletoe (Viscum album var.coloratum). A pharmaceutical composition aimed at inhibiting intravascular deposition of cholesterol and triglycerides by containing extracts from the leaves, stems, and fruits of the Korean mistletoe (Viscum album var.coloratum), or mixtures thereof as an active ingredient. The pharmaceutical composition according to claim 1 or 2, wherein the extract is contained in an amount of 0.01 to 50% by weight in a pharmaceutical composition and is formulated into tablets, capsules, pills, granules, or liquids. The aliphatic hydrocarbons, lower fatty acid esters according to claim 1, 2 and 3, in order to obtain an extract from each or a mixture of leaves, stems and fruits of the Korean mistletoe (Viscum album var.coloratum) used. An extracting method comprising extracting the extract extracted with a water-soluble organic solvent after degreasing with a nonpolar solvent such as oils, halogenated hydrocarbons, ethers, etc., and then extracting the concentrate with a low polar organic solvent dissolved in water. The sample is extracted with a water-soluble organic solvent according to claim 1, 2 or 3, in order to obtain an extract from each of the leaves, stems, and berries of the Korean mistletoe (Viscum album var.coloratum) used. After concentration under reduced pressure, the concentrate is degreased with a nonpolar solvent such as aliphatic hydrocarbons, lower fatty acid esters, halogenated hydrocarbons, ethers, and then extracted with a low polar organic solvent. The sample of crushed mistletoe according to claim 1, 2 and 3, to obtain an extract from each of the leaves, stems and berries of the Korean mistletoe (Viscum album var.coloratum) used or a mixture thereof. Extraction at 5 ~ 80 ℃, in this case the ultrasonic wave extractor, characterized in that the extraction method is adjusted to 10 to 50MHz.