KR20000007346A - Hyperlipemia blood curing agent extracted from doraji(korean name for) natural platycodon grandiflorum a. dc - Google Patents

Abstract

PURPOSE: An agent extracted from natural Doraji and a preparation of the hyperlipemia blood symptom is provided. CONSTITUTION: Roots of over 20 years old platycodon grandiflorum are dried and crushed to powder to be added with water and heated at 90-100°C for 4-6 hours, and extracts the essence twice in the course for filtration, the filtered liquid extract being added with an allowable herb medicine or herb extract selectively for a preparation.

Description

Hyperlipidemia treatment prepared with Jangsaeng Bellflower Extract

Field of invention

The present invention relates to an antihyperlipidemic agent prepared from Jangsaeng Bellflower Extract based on various pharmacological effects of Jangsaeng Bellflower (長 桔) over 20 years old produced according to the 'perennial bellflower cultivation method' of the Republic of Korea Patent No. 45791.

Background of the Invention

Bellflower (Gilkyung Platycodon grandiflorum A. DC) is a herbal medicine that has been used for respiratory diseases such as drainage, expectoration, bronchitis, asthma and anti-inflammation, and herbal medicines containing bellflower are 273 in consent and 49 in chemotherapy. It is known to have a variety of pharmacological action.

The major pharmacological component of bellflower is terpene-based saponins (prestigotin A, C, D, D ₆ , polygalacin D, D ₂ and 18 species), accounting for about 2% of the root. In animal experiments, terpene-based saponins are hemolytic, localized, antitussive, expectorant, central nervous inhibitory (sedative, analgesic, antipyretic), anti-inflammatory against acute and chronic inflammation, anti-allergic, anti-ulcer and gastric secretion , Anticholinergic to lower blood pressure by expanding blood vessels, lowering blood sugar, improving cholesterol metabolism [Igarashi, K., Sogoigaku, 3, 1 (1951) and Lee Eun-bang, Journal of Pharmacognosy, 5, 49 (1974 )]. In addition, steroidal compounds such as alpha-spinasterol, stigmas-7-enol, alpha-spinasterol glucoside and the like and polysaccharides such as inulin, platicodidine and betulin were also isolated.

In addition, the hot water and ethanol extracts of the bellflower inhibit the fungal apratoxin [Hitokoto, H., Morozumi, S., Wake, T., Sakai, S. and Ueno, I., Mycopathologia, 66, 161 (1979) ], The inulin fraction has phagocytosis [Nagao, T., Matsuda, H., Nambo, K. and Kubo, M., Shoyakugaku Zasshi, 40, 367 (1986)], the inulin, a fructose polymer, is a solid cancer It is known to have antitumor efficacy against ascites and ascites (Naga, T., Matsuda, H., Makata, K., Namba and Kubo, M., Shoyakugaku Zasshi, 40, 375 (1986)).

According to the invention utilizing the pharmacological properties of the bellflower, Japanese Patent Laid-Open No. 60-89427 discloses that the inulin fraction in 70% methanol extract of bellflower has 31-39% and 32-44, respectively, inhibitory effects against ascites and solid cancers in ICR mice. In combination with the chemotherapeutic drug mitomycin, it is shown that not only can suppress solid cancer by 61% but also suppress the side effects of mitomycin, such as weight loss and white blood cell count. Due to the excellent anti-tumor activity of the bellflower, Japanese Patent Application Laid-Open No. 2-172921 was administered to Enrlich ascites cancer cell lines using inulin obtained from tissue culture of bellflower to improve many difficulties in separating inulin from bellflower. Disclosed are the effects of the invention that result in inhibition rates and life-expansion rates of 140-145%. Japanese Patent Laid-Open No. 3-264534 discloses a 40% long-light extract as an alcohol absorption inhibitor.

Currently, about 30 kinds of herbal medicines containing bellflower are sold in Korea, China, Japan, etc., and five kinds of herbal medicines such as five-Yam Soon Ki-san, Tong-hwan, and Soon-gi-won are treatments for stroke, arthritis, etc. As a therapeutic agent for, Jamomile extract is used as a therapeutic agent for bronchitis, pulmonary tuberculosis, pleurisy and the like, and manokdan is used as a therapeutic agent for hypertension, arteriosclerosis and diabetes, respectively. Other herbal preparations containing bellflower are used for bronchial diseases such as asthma, expectoration, drainage, and Jinhae.

However, the bellflowers, which have been used in the herbal medicine and experiments until now, were grown for two to four years because the roots decayed when grown for more than four to five years. More than 20 years of perennial Jang Saeng Dora produced by the 'perennial bellflower cultivation method' recently patented No. 45791 is a patent protection herbal medicine is not used as a herbal medicine for sale at all.

Therefore, the present inventors have developed the use of Jangsaeng Bellflower as a therapeutic agent for hyperlipidemia by utilizing the fact that Jangsaeng Bellflower is significantly superior in pharmacological action compared to the common bellflower of 2-4 years old.

An object of the present invention is to provide the use as a herbal medicine of Jang Saeng Doraji having excellent pharmacological action and physiological activity compared to the common bellflower of 2-4 years old.

Another object of the present invention is to provide an antihyperlipidemic agent using Jangsaeng Bellflower Extract.

It is another object of the present invention to provide an herbal preparation that is nontoxic in vivo and has no other side effects.

The above and other objects of the present invention can be achieved by the present invention described below.

The present invention relates to the use of an extract prepared by preparing Jangsaeng Bellflower as a powder and then extracting it using hot water extraction or an organic solvent as a therapeutic agent for hyperlipidemia. In the following, the difference between the constituents and pharmacological action of the common bellflower and Jangsaeng bellflower will be examined in detail.

Common Bellflower and Jangsaeng Bellflower have no big difference in moisture, crude fat, mineral salt, etc. among common ingredients. The total amount of dietary fiber and the amount of irradiated phononine were detected as high as 3.1% and 0.4% in 22 years old, respectively. The total content of inulin in the constituent sugar components of the bellflower was almost unchanged from 70 to 73 mg / g, but there was a big difference in the degree of polymerization of fructose, the constituent sugar component of inulin. I.e. the higher the content of the Jang Saeng Doraji GF ₂ and GF ₃ shows the content of the general bellflower GF ₈ relatively higher in GF ₅ has been found that if asked a significant difference in the structure of inulin. In the above, G is glucose, F is fructose, which represents a component of inulin, and the number represents the number of fructose. As such, the fructose degree of fructose is detected with higher oligofractose with a lower fructose as the number of years of cultivation increases. These results are inferred to be related to the results of clinical trials that Jangsaeng Bellflower is more effective in hypertension, bronchus, diabetes, etc. than the common bellflower.

As inorganic salts, the contents of calcium (Ca), magnesium (Mg), and copper (Cu) are detected 3 to 10 times higher in Jangsaeng Bellflower than the common bellflower.

General and Jangsaeng bellflowers were extracted with 80% ethanol and 30% methanol, and analyzed by HPLC. The peaks, which are present only in Jangsaeng Doraji, were divided into solvents according to their polarity, and their physiological activities were examined. The effects were recognized in the petroleum ether and diethyl ether fractions. [Hashibong, Master Thesis, Gyeongsang National University (1996)].

Jangsaeng Doraji not only has a significant difference in the composition and composition, but also in pharmacological effects such as antibacterial activity, fat metabolism improvement, cancer cell adhesion inhibitory activity, immunopotentiation, hypoglycemic action, hypoglycemic action, etc. Excellent

80% ethanol and 30% methanol extract of Jangsaeng Doraji has free radical scavenging and antifungal activity and no cytotoxicity. Jangsaeng Bellflower shows broader and superior antibacterial spectrum than the common bellflower. Ethanol extract of Jangsaeng Doraji has a minimum inhibitory concentration (MIC) value of 5 mg / ml for bacteria and 2.5-10 mg / ml for fungi. Antimicrobial actives are most easily extracted at 50 ° C. and 95% ethanol concentration. When the 95% ethanol extract of Jangsaeng Doraji was again fractionated with solvent, the butanol fraction showed the highest antimicrobial activity, which is believed to be due to the saponin component, and the activity was detected in other solvent fractions. It is inferred to be abnormal. Among the antimicrobial active substances of Jangsaeng Doraji, it was isolated from ethyl acetate fraction and analyzed by structural analysis using several instruments. It was identified as glyceryl linoleate.

In addition, the blood glucose and lipid content of serum and liver are significantly reduced when dieting Jangsaeng Dorage powder or extract in hyperlipidemic rats. In particular, the 5% diet of Jangsaeng Doraji powder significantly reduced the total cholesterol and triglyceride levels in serum and liver, and the atherosclerosis index was also lower than that of the control group treated with Jangsaeng Doraji. These results suggest the possibility of prescribing Jangsaeng Doraji in the prevention and treatment of hypercholesterolemia or hyperlipidemia.

Jangsaeng bellflower extract of the present invention is effective in the treatment of diabetes mellitus is superior to the general bellflower lipids, such as blood sugar, serum, liver. Jangsaeng Doraji extract acts to significantly reduce serum total cholesterol and LDL levels in the body and increase serum HDL-cholesterol levels. Serum free cholesterol, cholesterol esters, triglycerides and phospholipids are also reduced to low levels and atherosclerosis is low.

When Jangsaeng Doraji extract is treated to cancer cell lines, the cancer cell adhesion inhibitory activity is excellent. When Jangsaeng Doraji methanol extract was treated to B16-F1 mouse melanoma cells to measure the binding capacity of laminin (laminin) when the concentration of the extract is more than 0.125 mg / ml will show 100% cancer cell adhesion inhibitory activity in cancer cell lines. It can be seen that Jangsaeng Doraji extract can inhibit cancer metastasis even at low concentrations.

In addition, the extract of Jangsaeng Doraji extract according to the polarity of the solvent to investigate the immune enhancing function shows the best effect in the aqueous layer. HPLC analysis of this aqueous layer showed the best immunostimulating activity in the inulin fraction of 20 inulin fructose polymerization. It is estimated that Jangsaeng Doraji correlates with inulin's fructose polymerization more than 5 times higher than the general bellflower.

Jangsaeng Doraji extract can be used for the treatment of inflammatory diseases such as rheumatoid arthritis because it has the ability to inhibit edema. It shows edema inhibitory activity similar to that of predisolone, an existing edema inhibitor. Incorporation of an acceptable herbal medicine or herbal extract that can enhance the efficacy of Jangsaeng Dorage will increase the inhibitory activity of edema due to synergy.

The present invention provides a drug using the excellent pharmacological activity of Jangsaeng Doraji. Jangsaeng Doraji extract which can be provided as a medicament of the present invention is prepared according to methods commonly used in the art. Jangsaeng Doraji extract can usually include hot water extract or organic solvent extract, these extracts may be used alone or may be prepared by adding a herbal medicine.

Generally, Jangsaeng Bellflower powder is prepared by drying Jangsaeng Bellflower so as to have a moisture content of 5% or less, pulverizing it, and then selecting a particle size of 0.6mm or smaller. The hot water extract is prepared by adding about 5-10 times of water to Jangsaeng Bellflower powder and selectively adding an acceptable herbal or herbal extract to the filtrate obtained by extracting twice for 4-6 hours at a temperature of 90-100 ° C. . In the case of the organic solvent extract, about three times the organic solvent is added to Jangsaeng Bellflower powder, and the filtrate obtained by extracting twice at room temperature is concentrated under reduced pressure to be prepared by selectively adding an acceptable herbal or herbal extract to the extract.

Alcohol may be used as the organic solvent, and methanol, ethanol, or the like may be preferably used. Acceptable herbal medicines include creation, mountain lions, gardens, sewage, baekbokyeong, and casualties.

Jangsaeng Doraji extracts of the present invention may be formulated or formulated as a dietary supplement by known methods using food hygiene or pharmacologically acceptable prostheses and pressurized into unit dosage forms or multi-dose containers. The dietary supplement or formulation may be in the form of an aqueous solution, suspension or emulsion, or may be in the form of extracts, powders, granules, tablets, capsules, and may contain conventional dispersants, suspensions or stabilizers.

The present invention will be embodied by the following examples, which are intended to illustrate the invention and are not intended to limit the scope of the invention.

Example

Example 1 Preparation of Jangsaeng Bellflower Extract Herbal Medicine

Jangsaeng bellflower is dried and pulverized to 5% or less of water content, and then the particle size is selected to be 0.6mm or less to prepare a powder. 10 times of water was added to Jangsaeng Bellflower powder and extracted twice at 4-100 hours at 90-100 ° C. to prepare a liquid product. In addition, the filtrate was further concentrated to prepare an extract, powder, granules, capsules and cyclic herbal medicines.

The ethanol extract was ground 1kg of Jangsaeng Bellflower, extracted twice with 4L of ethanol at room temperature for 2 days, and the filtrate was collected and concentrated under reduced pressure to obtain 125g of extract. The extract was used to prepare extracts, powders, granules, capsules and cyclic herbal medicines.

The extract of Jangsaeng Doraji may be prepared by adding an acceptable herbal medicine such as creation, mountain lion, raw paper, sewage, baekbokyeong, casualty and the like, or extract and concentrated herbal medicine extract as described above to increase the efficacy.

Example 2:

Effect of Feeding Jangsaeng Doraji on Serum and Hepatic Lipid Metabolism in Hyperlipidemic Rats

Sprague Dawley rats weighing 70 ± 5 g and 4 weeks old were fed a diet containing 20% lipid and 0.25% sodium cholate for 2 weeks in a basal diet containing 20% casein to induce hyperlipidemia. Six animals were divided into three groups, A, B, and C, for three weeks. Group A was fed only general feed (control), group B was fed a mixture of 5% common bellflower powder, and group C was fed a mixture of 5% Jangsaeng Bellflower powder. To compare the effects, normal diets were fed to 6 normal rats (group D) weighing 70 ± 5 g and 4 weeks old. Jangsaeng and Bellflower used in the experiment were lyophilized and powdered to less than 0.59mm, and then mixed and fed with conventional feed. As a result of the three-week spike, the food intake is shown in Table 1. On the last day of 3 weeks of experiment breeding, after choking for 7 hours, blood was collected by cardiac bleeding under ether anesthesia. Soy sauce was perfused with 0.9% physiological saline through the portal vein, and then drained by filter paper. After standing, centrifuged at 3,000 rpm for 15 minutes to obtain a serum. Blood glucose, cholesterol, triglyceride (triglyceride), phospholipid, glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaninase (GPT) and lactate dehydrogenase (LDH) in serum and liver were measured, and the results are shown in Table 1. These blood glucose, cholesterol, lipids, and enzyme activity were measured using a kit kit for measurement commonly used in the art.

ingredient Experimental group A group B group C group D group Weight gain (g / 3 weeks) 352 ± 6.1 330 ± 2.8 329 ± 5.2 346 ± 5.2 serum Blood sugar (mg / dl) 158 ± 5.5 156 ± 5.5 141 ± 1.4 142 ± 3.8 Total cholesterol (mg / dl) 262 ± 6.4 243 ± 2.3 166 ± 3.8 168 ± 6.0 LDL-cholesterol (mg / dl) 137 ± 4.3 124 ± 5.0 74.5 ± 3.0 94.4 ± 2.8 HDL-cholesterol (mg / dl) 62.7 ± 2.5 61.4 ± 2.5 65.9 ± 2.6 52.5 ± 2.3 Free cholesterol (mg / dl) 45.0 ± 0.6 44.2 ± 5.3 37.2 ± 1.5 31.8 ± 0.9 Triglycerides (mg / dl) 270 ± 12.0 256 ± 4.4 129 ± 5.0 174 ± 5.3 Phospholipids (mg / dl) 188 ± 3.3 171 ± 3.8 118 ± 5.4 160 ± 4.7 Arteriosclerosis index 3.2 ± 0.3 2.8 ± 0.2 1.5 ± 0.1 2.2 ± 0.2 GPT (Karmen unit / ml) 45.7 ± 2.1 40.2 ± 2.5 29.5 ± 5.1 35.6 ± 8.3 GOT (Karmen unit / ml) 90.1 ± 2.5 89.3 ± 3.1 80.7 ± 1.3 82.5 ± 3.3 LDH (Wroblewski unit / ml) 1,067 ± 23.7 1,347 ± 51.2 1,329 ± 53.5 1,474 ± 40.6 Soy sauce Total cholesterol (mg / g) 17.8 ± 2.8 16.1 ± 2.8 12.4 ± 3.2 8.0 ± 1.7 Free cholesterol (mg / g) 4.8 ± 0.4 5.4 ± 2.1 5.1 ± 0.4 4.0 ± 0.6 Triglycerides (mg / g) 88.1 ± 2.1 78 ± 3.5 46.0 ± 3.5 73.5 ± 2.3 Phospholipids (mg / g) 25.1 ± 4.1 25.0 ± 1.4 22.4 ± 3.0 23.7 ± 3.5

A group: Induce hyperlipidemia and feed group

Group B: Feed feed group containing 5% common bellflower powder

Group C: Feed feed group containing 5% Jangsaeng Bellflower powder

Group D: group not causing hyperlipidemia

Total cholesterol and triglyceride levels in serum and liver were significantly lower in the group that induce hyperlipidemia and dieted Jangsaeng Doraji powder (Group C) than the control group (Group A) or the group that fed General Bellflower Powder (group B). The figure was close to the normal group. Atherosclerosis index was lower than rats that did not cause hyperlipidemia. Therefore, it can be seen that Jangsaeng Doraji powder is effective in preventing and treating hyperlipidemia.

Herbal preparations prepared with more than 20 years old Jangsaeng Bellflower extract of the present invention is excellent in pharmacological and physiological activity compared to the general bellflower of 2-4 years old, and significantly improved lipid metabolism improvement in serum and liver compared to general bellflower Do. The antihyperlipidemic agent prepared with the extract of Jangsaeng Doraji of the present invention has no toxicity in vivo and has the effect of the invention without other side effects.

Simple modifications or changes of the present invention can be easily carried out by those skilled in the art, and all such modifications or changes can be seen to be included in the scope of the present invention.

Claims (3)

Jangsaeng Bellflower (20 years old or more perennial Bellflower) was dried and pulverized to prepare Jangsaeng Bellflower Powder; Water was added to the Jangsaeng Bellflower Powder and extracted by filtration twice for 4 to 6 hours at a temperature of 90 to 100 ° C; And Selectively adding an acceptable herbal medicine or herbal extract to the filtrate; Jangsaeng Bellflower hot water extract, characterized in that the step is prepared. Jangsaeng Bellflower (20 years old or more perennial Bellflower) was dried and pulverized to prepare Jangsaeng Bellflower Powder; About 3 times the organic solvent was added to the Jangsaeng Bellflower Powder, and extracted twice at room temperature and filtered; Concentrating the filtrate under reduced pressure to prepare an extract; And Selectively adding an acceptable herbal medicine or herbal medicine extract to the extract; Organic solvent extract of Jangsaeng Bellflower, which is prepared in a step. A therapeutic agent for hyperlipidemia, characterized in that it is prepared from Jangsaeng Bellflower Extract according to claim 1.