KR100891762B1 - Composition for vasorelaxant effect comprising a root extract of saururus chinenesis or active compounds isolated therefrom - Google Patents

Abstract

The present invention relates to a composition for vascular relaxation , comprising a compound selected from the group consisting of machilin D, south Neol D, and mixtures thereof, or Saururus chinenesis root extract comprising the same as an active ingredient. As the composition according to the present invention exhibits an excellent blood pressure lowering effect through vascular smooth muscle relaxation, it can be usefully used as a pharmaceutical composition or health food composition for the prevention and treatment of various cardiovascular diseases caused by the complications of hypertension and hypertension. have.

Description

Vascular relaxation composition comprising root extract or active ingredient isolated from the tritical sect root extract {COMPOSITION FOR VASORELAXANT EFFECT COMPRISING A ROOT EXTRACT OF SAURURUS CHINENESIS OR ACTIVE COMPOUNDS ISOLATED THEREFROM}

1 is a result of measuring the vascular smooth muscle relaxation effect by administering the trichophytium root extract of the present invention after the contraction of the thoracic aortic smooth muscle extracted from white rats treated with phenylephrine, a vasoconstrictor. ,

FIG. 2 shows the contraction of aortic smooth muscles extracted from the chest of a white rat with phenylephrine and then contracted with phenylephrine to relax vascular smooth muscle by administering the active ingredient isolated and purified from the three hundred sec root extract of the present invention. Is the result of measuring the effectiveness,

3 and 4 is a result of measuring the antihypertensive effect and heart rate change by oral administration of ethanol extract (10, 30 and 100 mg / kg) of three hundred seconds root to congenital hypertensive rats (SHR) for 2 weeks,

5 and 6 is a result of measuring the antihypertensive effect and heart rate change by oral administration of ethanol extract (100 mg / kg) of the root of the three hundred seconds for 6 weeks to congenital hypertensive rats (SHR).

The present invention relates to a composition for vascular relaxation, containing three hundred sec root extract, isolated from it, machilin di, South Neol di or mixtures thereof.

Blood pressure refers to the pressure of blood flow through the vessels, that is, arterial pressure. For some reason, systolic blood pressure is 120 mmHg (maximum blood pressure) or more and diastolic blood pressure is 80 mmHg (lowest blood pressure) or higher.

These hypertensions are basically associated with aberrant activity of the sympathetic nervous system, dysfunction of the cell membranes, impaired excretion of water and Na in the kidneys, decreased secretion of antihypertensive agents such as PGE ₂ , PGI ₂ , ANP and EDRF, or catecholamines. ) Or renin-angiotensin (renin-angiotensin), such as high blood pressure control function abnormalities are caused. That is, abnormalities of the nervous system, endocrine system, and cellular system lead to an increase in pressure of peripheral resistance blood vessels and cause hypertension. Hypertension is also often caused by complications such as kidney failure, arteriosclerosis, cerebral hemorrhage, stroke, blindness, heart failure and heart failure, rather than by itself.

To date, diuretics, beta blockers, calcium channel inhibitors, angiotensin converting enzyme inhibitors, and angiotensin receptor antagonists have been developed for the treatment of hypertension. However, since hypertension has been developed as a regulator for controlling hypertension, rather than curative treatment, there is a problem in that taking medication for a lifetime while starting hypertension treatment. Therefore, there is an urgent need for the development of new therapeutic agents that can alleviate side effects due to tissue specificity or resistance.

On the other hand, three hundred seconds (Sarurus chinensis ) is a perennial herb belonging to the three hundred genus (Saururus), a herb that has long been used as a folk medicine in China. In Chinese herbal medicine dictionary, three hundred seconds have been shown to be effective in eliminating fever and small seed detoxification, and are effective for several species, each of them, jaundice, sediment, sesame seeds, sesame seeds and sedimentary toxins. It is described in the herbal, primary natural metabolism dictionary, herbal milk, botanical name, algae, Yeongnam medicinal herb, Gwangseo medicinal herb, herb promotion and Honam medicinal herb. In addition, outposts, roots and leaves have been used in the private sector for the purpose of treatment of rubella, diuresis, species, gonorrhea, hepatitis, pneumonia, and poisoning.

The research on the components of the three hundred seconds has been mainly conducted on the flavonoids, alkaloids, amino acids, fatty acids, quinones and essential oils. Outpost contains methyl-n-nonyl ketone, stems contain high amounts of hydrolysable tannins, leaves contain quercetin, isoquercercitrin, abiculinin It has been reported that it contains hyperin, rutin and hydrolyzed tannins, and its roots contain various amino acids, organic acids, sugars, and the like.

Meanwhile, Chabal et al. Reported that sesquiterpene-based compounds exist from extracts of the same species, Saururus cernuus , a homogenous plant widely distributed in the wetlands of North America. ), SC-8, SC-9, manassantin A, manassantin B and saucerneol were separated from the extracts of the American trichophytium, and the structure was doubled. It was confirmed that Santin A has a neurosuppression inhibitory effect ( Tetrahedron Lett. , 24 (45): 4947-4950, 1983). In Korea, dimethyl telephthalate and quercetin were isolated and identified to have pharmacological and antimicrobial effects (Kwak Jae-wook, Ph.D. Thesis, Kyung Hee University, 1988), and also recently anti-cancer activity of three hundred seconds (Registration No. 10-0248942) And anti-inflammatory activity (Registration No. 10-0530274) has been filed.

The present inventors examined the vascular smooth muscle relaxation effect of the extracts of various herbal medicines including the root of the three hundred seconds, it was confirmed that the extract of the three hundred seconds root exhibits a potent vascular smooth muscle relaxation effect, and also from the extract of the root of three hundred seconds The present invention was completed by separating and purifying the active substances.

Accordingly, it is an object of the present invention to provide a pharmaceutical composition for vascular relaxation, containing 300 sec root extract as an active ingredient, which is useful for the prevention and treatment of hypertension and various cardiovascular diseases caused by inducing relaxation of vascular smooth muscle.

In addition, an object of the present invention is to provide a food having a vascular relaxation effect of the three hundred seconds root extract as an active ingredient.

In order to achieve the above object, the present invention provides a pharmaceutical composition for vascular relaxation, containing a compound selected from the group consisting of machinine di, South Neol di and mixtures thereof or three hundred seconds root extract comprising the same as an active ingredient.

Hereinafter, the present invention will be described in detail.

The pharmaceutical composition according to the present invention is characterized in that it contains three hundred sec root extract, Methylin Di, South Neol D, or mixtures thereof, which exhibit a blood pressure lowering effect through vascular smooth muscle relaxation, as an active ingredient.

First, the three hundred sec root extract according to the present invention can be prepared by solvent extraction of three hundred sec root or its dried product. Specifically, 2 to 200 times, preferably 10 to 30 times the organic solvent of the volume of the 300 seconds is added to the dried and finely divided 300 seconds roots, 1 to 20 days, preferably 5 to 10 days at 10 to 30 ℃ After extracting, filtering and concentrating under reduced pressure, a three hundred sec root extract can be prepared. At this time, the extraction solvent may be a solvent selected from the group consisting of ethanol, ethanol aqueous solution, methanol, methanol aqueous solution, butanol, dichloromethane, ethyl acetate, hexane and mixtures thereof, 80 to 100% ethanol or ethanol aqueous solution This is preferable.

In the present invention, chromatography is performed to isolate and purify the specific active ingredient exhibiting blood pressure lowering effect through vascular relaxation from the 300 sec root extract. Preferably, the chromatography is performed one or two times of reverse phase or silica gel column chromatography. Hexane / ethyl acetate (10: 1 to 1: 1) or methanol (50 to 90%) can be used as the mobile phase. At this time, the solvent used is eluted with a gradient gradient elution method to raise the concentration from nonpolar to polar, or from polar to nonpolar sequentially, and to obtain the desired active fraction by measuring the vascular relaxation effect of the collected isolates. can do.

Purification by chromatography of the active fraction exhibiting a vascular relaxation effect can be obtained machylin di of the formula (1) and South Neol di of the formula (2), which exhibits an excellent blood pressure lowering effect through vascular smooth muscle relaxation. In addition, it is possible to chemically synthesize machinine di and southneol di as necessary.

The trichophytium root extract of the present invention, Methylin Di, South Neol D, or mixtures thereof isolated from the above exhibits excellent blood pressure lowering effect through vascular smooth muscle relaxation, and thus can be used for the prevention or treatment of hypertension or hypertension complications.

The "hypertension" refers to a state in which the systolic blood pressure, the diastolic blood pressure or the average arterial pressure is continuously maintained higher than normal in a stable state, and the systolic blood pressure is continuously maintained at 120 mmHg or more and the diastolic blood pressure is 80 mmHg or more. Say when it will be.

"Hypertensive complications" refers to diseases caused by an abnormally elevated state of blood pressure, such as, but not limited to, coronary artery disease, cerebrovascular disease, peripheral vascular disease, aortic disease, renal dysfunction , Heart failure and visual impairment. Examples of coronary artery disease include angina pectoris and myocardial infarction, and examples of cerebrovascular diseases include stroke, cerebral hemorrhage, and cerebral infarction.

Furthermore, the pharmaceutical compositions according to the invention can be administered individually or in combination with other types of blood pressure lowering agents.

Pharmaceuticals having the above-mentioned functions by mixing, as an active ingredient, trichophytium root extract, isolated machinine di, southneol di, or mixtures thereof with a suitable pharmaceutically acceptable carrier or excipient according to conventional methods or by dilution with a diluent. The composition can be prepared. Examples of suitable carriers, excipients and diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, malditol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose , Microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. The pharmaceutical composition may further include fillers, anti-coagulants, lubricants, wetting agents, fragrances, emulsifiers, preservatives and the like.

The pharmaceutical compositions of the present invention may be formulated using methods well known in the art to provide rapid, sustained or delayed release of the active ingredient after administration to a mammal. The formulation may be in the form of tablets, pills, powders, sachets, elixirs, suspensions, emulsions, solutions, syrups, aerosols, soft or hard gelatin capsules, sterile injectable solutions, sterile powders and the like.

The pharmaceutical compositions of the invention can be administered via several routes including oral, transdermal, subcutaneous, intravenous or intramuscular. Typical daily dosages of the pharmaceutical compositions of the present invention, based on the active ingredient, 300 seconds root extract ranges from 10 to 100 mg / kg body weight, preferably 10 to 30 mg / kg body weight, Southneol di or a mixture thereof is in the range of 1 to 30 mg / kg body weight, preferably 1 to 10 mg / kg body weight, and may be administered one or several times. However, the actual dosage of the active ingredient should be determined in light of several relevant factors such as the route of administration, the age, sex and weight of the patient, and the severity of the disease, and therefore the dosage limits the scope of the invention in any aspect. It is not.

The present invention also provides a health promotion food or beverage composition which can prevent or alleviate hypertension and hypertension complications, including the trichophytium root extract, isolated Machinin di, South Neol di or mixtures thereof. do.

In order to achieve the above effects, as the food which can be added to the extract of the three hundred seconds root of the present invention, isolated Machinin di, South Neol di or a mixture thereof, for example, various foods, beverages, snacks, confectionery, gum , Ice creams, tea bags, instant teas, granules, flavorings, vitamin complexes, and other health supplements, but are not limited thereto.

The trichophyt root extract of the present invention, machinine di, south neol di or mixtures thereof isolated from the above may be added to the raw materials during food preparation or properly mixed with the cooked food to prepare the above-mentioned health promoting food or beverage. In this case, the content of the three hundred seconds root extract, isolated malicin di, South Neol di or mixtures thereof in the finally prepared food or beverage may be in the range of 0.01 to 30% by weight, respectively.

The pharmaceutical composition, or the health promoting food or beverage of the present invention may further include other medicinal herbs or extracts thereof that are pharmaceutically acceptable to enhance or supplement the desired effect, and representative examples of such herbal medicines include , Rhubarb, citron, and lotus root. The herbal medicine may be used in an amount of 0.01 to 50% by weight based on the total weight of the composition.

Hereinafter, the present invention will be described in more detail based on the following examples. However, the following examples are not intended to limit the invention only.

<Example 1> Preparation of three hundred vine extract and separation of active ingredient

1 kg of dried Triticale roots were chilled with 5 L of ethanol for 1 week, filtered, and the filtrate was concentrated under reduced pressure to obtain 127 g of ethanol extract.

Concentration elution method to raise the mixing ratio of hexane / ethyl acetate sequentially from 10: 1 to 1: 1 while flowing 16 g of the ethanol (EtOH) extract with a hexane / ethyl acetate mixed solution as a mobile phase at a flow rate of 3 ml / min. Silica gel column chromatography was performed and divided into a total of six fractions (first to sixth fractions). The fifth fraction was purified again by reversed phase chromatography (60-90% methanol) to separate 36 mg of malineline di from the 5-2 fraction, and again reversed phase chromatography (70-3). ˜90% methanol) to separate 7 mg of South Neol Di.

Machilin Di (Colorless Oil)

MS m / z : 344 [M] ⁺ ; ¹ H-NMR (CDCl _3, 300 MHz): δ 1.13 (3H, d, J = 5.7 Hz, H-9), 1.83 (3H, dd, J = 6.5, 1.2 Hz, H-9 '), 3.81 ( 3H, s, OCH ₃ ), 3.84 (3H, s, OCH ₃ ), 4.02 (1H, m, H-8), 4.53 (1H, d, J = 8.4 Hz, H-7), 6.10 (1H, dt , J = 15.6, 6.5 Hz, H-8 '), 6.31 (1H, m, H-7'), 6.76-6.87 (6H, m, Ar-H)

¹³ C-NMR (CDCl _3, 500 MHz): δ 150.8 (C-4 '), 146.9 (C-3'), 146.6 (C-3), 145.7 (C-4), 132.1 (C-1), 130.6 (C-1 ', 7'), 125.1 (C-8 '), 120.9 (C-6), 119.1 (C-6'), 118.9 (C-5 '), 114.3 (C-5), 109.6 (C-2 '), 109.4 (C-2), 84.3 (C-7), 78.6 (C-8), 56.0 (-OCH ₃ ), 18.6 (C-9'), 17.2 (C-9)

South Neol Di (Colorless Powder)

HRFABMS m / z : 554.2751 (C ₃₁ H ₃₆ O ₈ NH ₄ , calc. 554.2754); ¹ H-NMR (CDCl _3, 300 MHz): δ 0.70 (6H, d, J = 5.7 Hz, H-9, 9 '), 1.17 (3H, d, J = 6.3 Hz, H-9''), 2.27 (2H, m, H-8, 8 '), 3.88 (3H, s, OCH ₃ ) _, 3.89 (3H, s, OCH ₃ ), 3.93 (3H, s, OCH ₃ ), 4.13 (1H, m, H-8``), 4.63 (1H, d, J = 8.4 Hz, H-7``), 5.42 (1H, J = 6.3 Hz, H-7), 5.44 (1H, J = 6.0 Hz, H- 7 '), 5.95 (2H, -OCH ₂ O-), 6.76-6.99 (9H, m, Ar-H)

¹³ C-NMR (CDCl _3, 500 MHz): δ 150.7 (C-3 '), 149.2 (C-3``), 149.0 (C-4''), 147.7 (C-3), 146.6 (C- 4), 146.5 (C-4 '), 136.8 (C-1'), 135.5 (C-1), 132.7 (C-1``), 120.2 (C-6 ''), 119.5 (C-6) , 118.9 (C-5 '), 118.8 (C-6'), 110.9 (C-5 ''), 110.3 (C-2 '), 110.2 (C-2''), 108.0 (C-5), 107.1 (C-2), 101.1 (-OCH ₂ O-), 84.3 (C-8``), 83.9 (C-7), 83.7 (C-7 '), 78.6 (C-7''), 56.0 (-OCH <sub>3</sub> ), 44.1 (C-8 '), 44.0 (C-8), 17.2 (C-9``), 14.9 (C-9, 9')

On the other hand, water and hexane was used instead of ethanol as an extraction solvent, and water extracts and hexane extracts of the root of 300 seconds were prepared in the same manner as the method of preparing the ethanol extract of the root, respectively. Ethanol, water and hexane extracts of the leaves were prepared, respectively.

Example 2 Determination of Vascular Relaxation Effect of Three hundred Second Extract and Active Ingredients Isolated from the Extract

The extract of three hundred seconds obtained in Example 1, and the extraction of vasculature-releasing effects (ie, the protective effect against vasoconstrictive agents as a blood pressure lowering effect) of each of the extracts of malinelin and south neool, were measured as follows.

Sprague-Dawley (SD, male) rats (Orient, Korea) are clean animal breeding rooms with automatic adjustment of contrast at constant temperature (22.5 ± 1 ℃), humidity (55 ± 5%), and 12 hour intervals. After stabilizing at least for 2 weeks at was used in the experiment. After striking and stunning the back of the SD rat, the carotid artery was cut and blood was lost. After the incision of the rib cage, the descending aorta was quickly removed and the adipose tissue and surrounding tissue were carefully removed so as not to damage the endothelium. From this, the blood vessels were cut into 2-3 mm lengths (Krebs-Henseleit or Krebs' bicarbonate buffer: NaCl 118.0 mM, KCl 4.7 mM, CaCl ₂ 2.5 mM, MgSO ₄ 1.2 mM, KH ₂ PO ₄ 1.2 It was suspended in a tissue chamber containing 25.0 mM of NaHCO ₃ and 11.0 mM of glucose, Junsei, Japan, hereinafter referred to as "KH buffer". At this time, the temperature in the chamber was maintained at 37 ℃, saturated with O ₂ / CO ₂ mixed gas (O ₂ : CO ₂ = 95: 5) to maintain a pH of 7.4. Equilibration was carried out for 90 minutes at 2 g of initial tension and exchanged with fresh KH buffer at 15 minute intervals. Vasoconstriction / relaxation can be achieved by using a force displacement transducer (Grass FT03, Grass, USA) with a chart recorder (Multicorder MC 6625), Hugo Swine. (Hugo Sachs), Germany).

To adapt the bleeding blood vessels in the tissue chamber, it was shrunk with 0.3 μM of phenylephrine (Sigma-Aldrich Co., USA) and washed three times over 45 minutes with KH buffer. It was. After contraction of the bleeding vessel again with phenylephrine to reach a stable state, 1 μM acetylcholine chloride (acetylcholine chloride, Sigma Aldrich, USA) was added to confirm that the blood vessels were completely relaxed, indicating that the vascular endothelium was not damaged. It was. Samples used in this experiment (extract of 300 seconds, machilin di, South Neol di each) were dissolved in dimethyl sulfoxide (DMSO) and diluted with KH buffer solution, DMSO concentration at the highest concentration was 0.03% It was. All drugs and reagents used in the experiment were prepared just before the start of the experiment.

Vascular relaxation measurement was performed by adding a sample to the blood vessels contracted by phenylephrine by concentration accumulation method (1, 3, 10 and 30 µg / ml) to measure the degree of relaxation of blood vessels. At this time, the results of the experiment showed the degree of relaxation based on the contraction state by phenylephrine as a percentage (%), and obtained the EC ₅₀ value (concentration to relax 50%) through linear regression analysis in Table 1 below. Each of the vascular smooth muscle relaxation effects is shown in FIGS. 1 and 2 as a graph.

As shown in Figure 1, among the three hundred extract ethanol extract of three hundred seconds root, three hundred second root hexane extract and three hundred second leaf hexane extract relaxes the blood vessels contracted by the vasoconstrictor concentration-dependent, the ethanol extract of three hundred seconds root Indicated. In addition, as shown in FIG. 2, it can be seen that both the malineline di and south neool di separated and purified from the root extract of Hundred seconds induce vascular relaxation and exhibit excellent vascular relaxation effects.

Example 3 Determination of Antihypertensive Effect of Ethanol Extract of Trituses chinensis

The antihypertensive effect of the ethanol extract of the root of 300 seconds obtained in Example 1 was measured as follows.

Spontaneously hypertensive rats (SHR, male, 13-14 weeks of age) were found in Charles River Laboratories (USA, primary experiment) and Charles River Laboratories Japan Inc. Purchased from Japan (Secondary experiment, confirm study) and used in experiments after stabilization in clean animal kennels with automatic adjustment of contrast at constant temperature (22.5 ± 1 ° C), humidity (55 ± 5%), and 12-hour intervals. . Blood pressure and heart rate were measured using a tail-cuff method, a method of measuring blood pressure from the tail of an experimental animal, using a photoplethysmograph (Model 31, IITC Life Sci., Woodland Hills). , CA, USA). For stable blood pressure measurement, the experimental animals were stabilized in a constant temperature box at 32 ° C. for about 5 to 10 minutes, and blood pressure measurement training was performed for 1 to 2 weeks before starting the experiment. SHR used only systolic blood pressure of 170 mmHg or more.

In the first experiment, the control group (1% Arabian gum), ethanol extract 10, 30 and 100 mg / kg administration group of 300 seconds root and captopril (Sigma Co., USA) as a control group The group was divided into 5 groups, such as the 10 mg / kg administration group, and divided into 8 groups in each group so that there was no significant difference in the reference blood pressure between the groups. Each test substance was suspended using 1% Arabian gum and then orally administered using sonde. All test substances used in the experiment were prepared immediately before use. Blood pressure was measured 2.5 hours after oral administration of the test substance, and the day before the start of the experiment and 1, 2, 3, 5, 7, 10 and 14 days after the test substance administration.

The second experiment was carried out to reconfirm the results of the first experiment. As the experimental group, the control group (1% Arabian gum), the ethanol extract (100 mg / kg) administered from the root of 300 seconds, and the control captopril (30 mg / kg) The group was divided into four groups, the WKY rat (Wistar-Kyoto rat; Charles River Laboratories Japan Inc .; normal blood pressure rat; 1% Arabian gum), the control group and the SHR control group. Animals were similarly divided into 12 groups in WKY group and 8 in each group. Each test substance was suspended using 1% Arabian gum and then orally administered using sonde. All test substances used in the experiment were prepared immediately before use. Blood pressure was measured 2.5 hours after oral administration of the test substance, and the day before the start of the experiment and 1, 2, 7, 14, 21, 28, 35 and 42 days after the test substance administration. All experimental results were expressed as mean ± Standard Error of Measurement (SEM), and statistical analysis of the experimental results was performed using the Sigma Stat (Jandel Co., USA) program, t-tested (unpaired). And one-way analysis of variance (ANOVA), and the secondary test was a Dunnett multiple comparisons test.

As a result of the first experiment, the change in blood pressure after oral administration of ethanol extract of the root of the test substance 300 sec to SHR (the blood pressure after administration of the test substance minus the blood pressure before administration of the test substance; mmHg) is shown in FIG. 3. . First, the reference blood pressure in the control group (1% Arabian gum), the ethanol extract 10, 30 and 100 mg / kg of the 300 seconds root and the control captopril 10 mg / kg group was 188 ± 1.7, 187 ± 4.8, 190, respectively. There was no significant difference between the groups as ± 4.2, 190 ± 4.3 and 187 ± 3.9 mmHg. The ethanol extract group in the root of 300 seconds showed blood pressure drop in dose-dependent manner, especially in the 100 mg / kg group, the blood pressure was significantly lowered after 5 days of administration, which was administered 10 mg / kg of the control compound captopril. It showed a similar effect as when done.

On the other hand, the amount of heart rate change after administration of the test substance (the heart rate after administration of the test substance minus the heart rate before administration of the test substance; heart rate / minute) is shown in FIG. The reference heart rates in the control group, the ethanol extract 10, 30 and 100 mg / kg administration group and the control captopril 10 mg / kg control group were 391 ± 10.8, 383 ± 13.2, 407 ± 15.0, 400 ± 8.1 and There was no significant difference between groups as 395 ± 14.4 beats / min. All groups, such as 10, 30 and 100 mg / kg ethanol extract and control group captopril 10 mg / kg, showed no significant difference in heart rate change compared to the control group.

As a result of the second experiment, the change in blood pressure after oral administration of the ethanol extract of the root of the test substance 300 sec to SHR (the blood pressure after administration of the test substance minus the blood pressure before administration of the test substance; mmHg) is shown in FIG. 5. . First, the baseline blood pressures in the control group (1% Arabia gum), the 100 mg / kg ethanol extract of the root of 300 seconds and the control captopril 30 mg / kg, were 190 ± 5.7, 199 ± 4.6 and 189 ± 3.6 mmHg, respectively. There was no significant difference between the groups, and systolic blood pressure was 142 ± 3.6 mmHg in WKY rats. Blood pressure was measured at weekly intervals for 42 days. As time passed, systolic blood pressure of WKY rats tended to decrease gradually, and the SHR control group showed a gradually rising blood pressure. When administration of 100 mg / kg ethanol extract of the root of the 300 seconds, blood pressure dropped about 20% compared to the control group 7 days after the administration, which continued until 42 days after the end of the experiment. When control group captopril was administered at a high dose of 30 mg / kg, it showed a significant blood pressure lowering effect than the control group.

On the other hand, the heart rate change after administration of the test substance is shown in FIG. The reference heart rate in the control group, 100 mg / kg ethanol extract of the root of Trichophyte and 10 mg / kg of the control captopril was 424 ± 10.0, 420 ± 7.9 and 406 ± 7.8 beats / min, respectively. There was no difference. At this time, compared to the control group did not show a statistically significant difference in all the administration group, in the captopril administration group the heart rate increased by about 30 to 40 beats / min due to the blood pressure drop reflex action.

The pharmaceutical preparations or foods were prepared as follows using the trichophytium root extract of the present invention or the active ingredient isolated therefrom.

Production Example 1 Powder

The powders were prepared by mixing the following ingredients and then filling the airtight cloth according to a conventional powder preparation method:

3 g of root dried extract or active ingredient isolated and purified from it

1 g lactose

Preparation Example 2 Tablet

The tablets were prepared by mixing the following ingredients and then tableting according to the conventional tablet preparation method:

100 grams of dried root extract or active ingredient isolated and purified from it

100 mg corn starch

Lactose 100 mg

2 mg magnesium stearate

Preparation Example 3 Capsule

The capsules were prepared by mixing the following ingredients and filling the gelatin capsules according to a conventional capsule preparation method:

100 grams of dried root extract or active ingredient isolated and purified from it

100 mg corn starch

Lactose 100 mg

2 mg magnesium stearate

<Manufacture example 4> Wire type

Brown rice, barley, glutinous rice, and yulmu were alphad by a known method, and then dried and roasted to make a powder having a particle size of 60 mesh. Black beans, black sesame seeds, and perilla were also steamed and dried in a known manner, and then ground to a powder having a particle size of 60 mesh.

The trichophyt root extract of the present invention was concentrated under reduced pressure in a vacuum concentrator, and the dried product obtained by drying with a spray hot air dryer was pulverized into a particle size of 60 mesh with a grinder to obtain a trichophytium root extract dry powder.

Granules were prepared by combining the dry powders of the grains, seeds, and trichophytium root extracts prepared above in the following proportions.

Cereals: Brown rice 30% by weight, barley 15% by weight, barley 20% by weight, glutinous rice 9% by weight,

Seeds: perilla 7% by weight, black beans 8% by weight, black sesame 7% by weight,

Three hundred percent root extract dry powder 3% by weight, ganoderma lucidum 0.5% by weight, turmeric 0.5% by weight

Preparation Example 5 Chewing Gum

Chewing gum was prepared in a conventional manner by combining 20% by weight of gum base, 76.9% by weight of sugar, 1% by weight of perfume, and 2% by weight of water, and 0.1% by weight of Trichophyt root extract of the present invention.

Production Example 6 Candy

Candy was prepared in a conventional manner by combining 60% by weight of sugar, 39.8% by weight of starch syrup, and 0.1% by weight of fragrance, and 0.1% by weight of the extract of Trichophytium root.

Production Example 7 Biscuits

Force 25.59% by weight, 22.22% by weight of gravity, 4.80% by weight, white salt 0.73% by weight, 0.78% by weight, palm shortening 11.78% by weight, ammonium 1.54% by weight, 0.17% by weight sodium bisulfite 0.16% by weight , Rice flour 1.45%, Vitamin B₁0.0001%, Vitamin B₂0.0001%, Milk flavor 0.04%, Water 20.6998%, Whole milk powder 1.16%, Substitute milk powder 0.29%, Monobasic calcium phosphate 0.03% , Biscuits were prepared in a conventional manner by combining 0.29% by weight of spraying salt and 7.27% by weight of spray oil with 1% by weight of the extract of Trichophyte root.

<Manufacture example 8> Healthy drink

0.26% by weight of honey, 0.0002% by weight of thioctoamide, 0.0004% by weight of nicotinic acid, 0.0001% by weight of sodium riboflavinate, 0.0001% by weight of pyridoxine hydrochloride, 0.001% by weight of inositol, 0.002% by weight of orthoic acid and 98.7362% by weight of water 1300% by weight of the root extract of three hundred seconds was prepared in a conventional manner for a healthy drink.

Preparation Example 9 Health Supplement

55% by weight of spirulina, 10% by weight of guar gum enzyme digestion, 0.01% by weight of vitamin B ₁ hydrochloride, 0.01% by weight of vitamin B ₆ hydrochloride, 0.23% by weight of DL-methionine, 0.7% by weight of magnesium stearate, 22.2% by weight of lactose and 1.85% by weight of corn starch % And 10% by weight of the extract of the root of the three hundred seconds of the present invention to prepare a tablet-type health supplement in a conventional manner.

As described above, the composition containing the three hundred seconds root extract according to the present invention, isolated and purified from the Machilin di, South Neol di as an active ingredient has excellent blood pressure lowering effect through the smooth muscle relaxation of the blood vessels, hypertension In addition to the prevention and treatment of, it can be useful for the prevention and treatment of various cardiovascular diseases such as complications caused by hypertension, namely stroke, arteriosclerosis, ischemic heart disease and congestive heart failure.

Claims (7)

delete delete delete South Neol D (saucerneol D) and a health functional food for improving hypertension containing Saururus chinenesis root ethanol extract containing the same. The method of claim 4, wherein Health functional food, characterized in that the food is in the form of a drink. delete delete

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