KR20150132988A - A composition comprising an extract of Dendropanax morbifera for preventing and treating hypertension - Google Patents

Abstract

The present invention relates to a composition containing Dendropanax morbifera extracts as an active ingredient. More specifically, it is identified that the extracts in the present invention has a strong inhibitory effect on hypertension in animal models of hypertension through animal tests including tests on the effects of the extracts in the present invention on the blood pressure, and the serum levels of angiotensin II, angiotensin converting enzyme (ACE), and aldosterone. Therefore, the composition is useful as a pharmaceutical composition or health functional food for preventing and treating hypertension.

Description

[0001] The present invention relates to a composition for preventing and treating hypertension,

The present invention provides a composition for the prevention and treatment of hypertension, which comprises extracts of Aspergillus oryzae as an active ingredient.

[Document 1] Reddi AS. Resistant hypertension: is renal denervation of the current treatment of choice. Clin Exp Hypertens (2014)

[Literature 2] Hans R., et al .. Essential Hypertension: Renin and Aldosterone, Heart Attack and Stroke. N Engl J Med 286: 441-449 (1972)

[3] Kim HR, et al .. Chemical characteristics of the leaves and seeds of Korean Dendropanax ( Dendropanax morvifera Lev .). J. Korean Soc. Agric. Chem. Biotechnol. 43: 63-66 (2000) Park SN, et al. Cellular antioxidant activity and whitening effects of dendropanax morbifera leaf extracts, Korean Society for Microbiology and Biotechnology, 41 (4): 407-415 (2013).

[Document 4] Kurtz TW, et al., Biological variability in Wistar-Kyoto rats. Implications for research with the spontaneously hypertensive rat. Hypertension 10 (1): 127-31 (1987)

&Quot; Hypertension " means a stable systolic blood pressure of 140 mmHg or greater or a diastolic blood pressure of 90 mmHg or greater. Hypertension is divided into primary hypertension (essential hypertension) in which no specific cause is found and secondary hypertension (secondary hypertension) which is caused by specific cause disease. Primary hypertension accounts for more than 90% of total hypertension. Although it is not possible to find any specific cause, it is known that multiple causes are the most common and genetic factors are important. The main causes of secondary hypertension include acute and chronic renal failure, drug abuse, acute stress, aortic stenosis, acromegaly, and multiple neuropathy. It is important to maintain and maintain normal blood pressure through proper lifestyle and eating habits since hypertension is difficult to cure once it has occurred (Clin Exp Hypertens (2014) ).

The mechanism by which the human body regulates blood pressure is controlled by neurogenic regulation, humoral control, hormones and neurotransmitters. The renin-angiotensin-aldosterone system (RAAS), the most representative blood pressure control system, is a system that maintains the extracellular fluid homeostasis by the mechanism of humoral regulation. When the extracellular fluid volume decreases or arterial blood volume decreases, blood pressure of the renal arteries decreases, so renal vasculature cells are stimulated to release renin. Angiotensinogen in plasma is activated and converted to angiotensin I by the action of renin, and is further converted to angiotensin II (Angiotensin II) by angiotensin converting enzyme (ACE) ). Activated angiotensin II (Angiotensin II) stimulates the sympathetic nerves or adrenal glands to stimulate the release of catecholamine, thereby increasing blood pressure and promoting the release of aldosterone, the adrenocortical hormone. Secreted aldosterons stimulate reabsorption of sodium ions and water in the kidneys, thereby increasing extracellular fluid and increasing blood pressure. (Hans R., et al. Essential Hypertension: Renin and Aldosterone, Heart Attack and Stroke. N Engl J Med 286: 441-449 (1972)).

It is a dicotyledonous plant native to the southern coastal area of Korea and Jeju Island. It is an evergreen tree of the Araliaceae ( Dendropanax morbifera ) is a species that does not tolerate fallen leaves in the winter. If you bruise the bark, yellow resinous liquid comes out. The physiological activities such as anticancer activity and antioxidant activity of Hwangchulchu extract have been reported to be limited and they have been used in foods such as food additives and health functional supplements (Kim HR, et al .. Chemical characteristics of the leaves and the seeds (2000), Park SN, et al .. Cellular antioxidant activity and whitening effects of dendropanax morbifera leaf extracts, Korea (Korean) Dendropanax morphifera Lev ., Korean Society for Applied Biological Chemistry Microbiology Biotechnology Journal, 41 (4): 407-415 (2013)).

There is currently no disclosure or teaching of the hypertensive inhibitory effect of Horticultural extracts, especially fractions, anywhere in this document.

Therefore, the present inventor has found an excellent activity of the fractions derived from Fusarium oxysporum sp. While investigating the activity against natural products in order to find an antihypertensive agent, thereby completing the present invention.

In order to achieve the above object, the present invention provides a pharmaceutical composition for prevention and treatment of hypertension, which contains an extract of Aspergillus oryzae as an active ingredient.

Also, the present invention provides a health functional food for prevention and improvement of hypertension, comprising the extract of Aspergillus oryzae as an active ingredient.

As described above, the extract is a crude extract, a polar solvent-soluble extract, or a non-polar solvent-soluble extract.

The crude extract as defined herein may be dissolved in a solvent selected from water containing purified water, a lower alcohol having 1 to 4 carbon atoms such as methanol, ethanol, and butanol, or a mixed solvent thereof, preferably a water and ethanol mixed solvent, (V / v) ethanol, more preferably 10 to 50% (v / v) ethanol.

The non-polar solvent soluble extract fractions defined herein comprise extract fractions which are soluble in non-polar solvents which have been purified from the crude extracts of the present invention and purified only in extracts soluble in hexane, methylene chloride, chloroform or ethyl acetate, preferably ethyl acetate solvent.

The polar solvent-soluble extract as defined herein is prepared by removing the non-polar solvent-soluble fractions from the crude extract and washing with water, methanol, butanol or a mixed solvent thereof, preferably water or butanol, more preferably, And one extracted fraction.

Hypertension as defined herein includes essential hypertension, secondary hypertension, preferably essential hypertension.

The perennial tree as defined herein includes whole parts of branches, leaves, roots, etc., preferably branches or root parts.

Hereinafter, the present invention will be described in more detail.

The extracts of the present invention can be obtained by the following production methods.

For example, the present invention will be described in detail below.

The Horticultural Extract of the present invention can be prepared as follows. Water and ethanol mixed solvent, more preferably 10% ethanol, and more preferably 10% ethanol, water, methanol, ethanol, butanol or the like, or a mixed solvent thereof, Followed by ultrasonic extraction, hot water extraction, room temperature extraction, or extraction at 30 ° C to 150 ° C, preferably 40 ° C to 100 ° C, for 30 minutes to 48 hours, preferably 1 hour to 12 hours, The crude extract of the present invention can be obtained by filtration, concentration under reduced pressure, and drying the extract obtained by performing the reflux extraction method, preferably the hot water extraction method, repeatedly about 1 to 20 times, preferably 2 to 10 times.

The polar solvent or the non-polar solvent soluble extract of the present invention may further contain about 0.0005 to 50 times, preferably 0.05 to 5 times the volume (v / w%) of the crude extract, preferably 10 to 90% ), Followed by a conventional fractionation using hexane, methylene chloride, chloroform, or ethyl acetate, preferably an ethyl acetate solvent, followed by extraction with hexane, methylene chloride, chloroform or ethyl acetate, preferably ethyl acetate A nonpolar solvent-soluble extractable fraction which is soluble in a nonpolar solvent; And the non-polar solvent-soluble extract fractions are removed to obtain polar solvent-soluble extract fractions soluble in a polar solvent such as butanol and water.

The present inventors conducted experiments on the blood pressure of experimental animals, the effect on serum angiotensin II concentration, and the concentration of serum angiotensin converting enzyme (ACE) The present inventors confirmed that the samples of the present invention exhibit a strong hypertension inhibitory effect on hypertensive experimental animals through animal experiments such as an experiment on the effect on the concentration of aldosterone of serum, Or health functional foods.

Accordingly, the present invention provides a pharmaceutical composition and a health functional food for prevention and treatment of hypertension containing the extract of Wuchulia officinalis obtained by the above production method as an active ingredient.

Also, it is a medicinal herb that has been used for a long time as an edible or herbal medicine, and thus the extract of the present invention has no toxicity and side effects.

The pharmaceutical composition of the present invention contains 0.1 to 50% by weight of the above extract relative to the total weight of the composition.

The pharmaceutical compositions comprising the extract of the present invention may further comprise suitable carriers, excipients and diluents conventionally used in the production of pharmaceutical compositions.

Examples of carriers, excipients and diluents that can be included in the composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

The composition containing the extract of the present invention may be formulated in the form of powders, granules, tablets, capsules, oral preparations such as suspensions, emulsions, syrups and aerosols, external preparations, suppositories and sterilized injection solutions, Can be used.

More specifically, when formulating the composition, it can be prepared using a diluent or an excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, a surfactant, and the like. Solid formulations for oral administration include tablets, pills, powders, granules and capsules, 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. Liquid preparations for oral use include suspensions, solutions, emulsions and syrups. In addition to water and liquid paraffin which are commonly used simple diluents, various excipients such as wetting agents, sweetening agents, fragrances and preservatives may be included. have. 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 and vegetable oils such as olive oil, and injectable esters such as ethyl oleate. As a suppository base, witepsol, macrogol, tween 61, cacao paper, laurin, and glycerol gelatin can be used.

The preferred dosage of the extract of the present invention varies depending on the condition and the weight of the patient, the degree of disease, the type of drug, the administration route and the period of time, but can be appropriately selected by those skilled in the art. However, for the desired effect, the extract of the present invention may be administered in an amount of 0.0001 to 100 mg / kg, preferably 0.001 to 100 mg / kg, once or several times per day. In the composition, the extract of the present invention may be formulated in an amount of 0.0001 to 50% by weight based on the total weight of the total composition.

The pharmaceutical composition of the present invention can be administered to mammals such as rats, mice, livestock, humans, and the like in various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine and intracerebroventricular injections.

Also, the present invention provides a health functional food for prevention and improvement of hypertension, comprising the extract of Aspergillus oryzae as an active ingredient.

The extract of the present invention can be used variously for medicines, foods and beverages for the prevention and treatment of a target disease. Examples of foods to which the extract of the present invention can be added include various foods, beverages, gums, tea, vitamin complexes, and health supplement foods, and they can be used in the form of powders, granules, tablets, have.

The extract of the present invention can be added to food or beverage for the purpose of prevention and treatment of a target disease. At this time, the amount of the extract in food or beverage is generally 0.01 to 15% by weight of the total food weight of the health food composition of the present invention, and 0.02 to 30 g of 100% Can be added at a ratio of 0.3 to 10 g.

The health beverage composition of the present invention may contain various flavors or natural carbohydrates such as ordinary beverages as an additional ingredient, as long as it contains the extract as an essential ingredient at the indicated ratio, and there is no particular limitation to the liquid ingredient. Examples of the above-mentioned natural carbohydrates include monosaccharides such as disaccharides such as glucose and fructose, polysaccharides such as maltose, sucrose and the like, such as dextrin, cyclodextrin and the like , Xylitol, sorbitol and erythritol. Natural flavors (tau martin, stevia extracts (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.) can be advantageously used as flavors other than those described above The ratio of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the composition of the present invention.

In addition to the above, the extract of the present invention can also be used as a flavoring agent such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, coloring agents and aging agents (cheese, chocolate, etc.), pectic acid and its salts, Salts, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated beverages and the like. In addition, the extract of the present invention may contain natural fruit juice and pulp for the production of fruit juice drinks and vegetable drinks. These components may be used independently or in combination. The proportion of such additives is not so critical, but is generally selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.

As described above, the extract of the present invention can be used to test the effect on the blood pressure of experimental animals, the effect on serum angiotensin II (Angiotensin II) concentration, the serum angiotensin converting enzyme (ACE) The present inventors confirmed that the samples of the present invention exhibit a strong hypertensive inhibitory effect on hypertension-induced experimental animals through animal experiments such as an experiment on the concentration of the compound and an effect on the concentration of aldosterone of serum, It was confirmed to be useful as a pharmaceutical composition or health functional food.

FIG. 1 is a view showing a manufacturing process for separating the extract of Hwangchujang;
FIG. 2 is a graph showing the effect of extracts or fractions of Wortmannia crassifolia on blood pressure;
FIG. 3 is a graph showing the effect of extracts or fractions of Wortmannia crassifolia on serum angiotensin concentration;
FIG. 4 is a graph showing the effect on the aldosterone concentration of the extract of Fusarium oxyspermum or fractions thereof.

Hereinafter, the present invention will be described in detail with reference to the following examples and experimental examples.

However, the following Examples and Experimental Examples are merely illustrative of the present invention, and the contents of the present invention are not limited by the following Examples, Reference Examples and Experimental Examples.

Example 1. Yellowwood Crude extract  Produce

1-1. ethanol Crude extract  Produce

(2 kg) of dried Hwangbuchun (Hambak Re-Farm, Jeju Island, hbjfarm / com) was cut into 0.5 cm size and crushed into an extraction vessel (Ilshin Lab Co., Ltd, FD8512). 20 L of ethanol and 20 L (Extraction temperature: 45 ~ 55 ℃) and filtered with a filter paper (3M paper) to obtain an extract liquid phase. In order to prevent excessive sugar components from being extracted from the functional components, the extraction was carried out once for 6 hours. Subsequently, the obtained extract solvent was concentrated under reduced pressure using a vacuum evaporator (Sunil EYELA, Rotatory evaporator, N-1N) to obtain 96 g of ethanol extract (Hereinafter referred to as " DME ").

1-2. water Crude extract  Produce

(2 kg) was cut into 0.5 cm size and pulverized. Then, 20 g of distilled water was added to the extraction vessel (Ilshin Lab Co., Ltd, FD8512), and the mixture was heated in a distillation circulating apparatus 95 ~ 100 ℃) and filtered with 3M paper to obtain an extract liquid phase. Extraction was carried out once for 6 hours to prevent excess sugar components from being extracted from the functional ingredients. The obtained extract solvent was then concentrated under reduced pressure using a vacuum evaporator (Sunil EYELA, Rotary evaporator, N-1N) to obtain 138 g of water extract (Hereinafter referred to as " DMW ").

Example 2. Yellowish wood polar solvent and Nonpolar solvent  Preparation of soluble extract (see Figure 1)

2-1. From the extract of Hwangchu - Hexane Fraction  Produce

A total of 1.6 L of distilled water was suspended in ethanol extract (80 g) obtained from Example 1 and suspended in a fractionating funnel. 1.6 L of n-hexane was added to extract the fraction. About one hour later, the n-hexane fraction was extracted from the supernatant to obtain n-hexane fraction. The fractionation procedure was repeated 3 times, after which the supernatant was concentrated under reduced pressure to give 6.8 g of n-hexane fraction. (Hereinafter referred to as " DMHE ").

2-2. From ethyl acetate extract Fraction  Produce

The distilled water fraction obtained in the step of obtaining the n-hexane fraction was suspended in 1.5 L of distilled water, suspended in a fractionating funnel, and extracted with 1.5 L of ethyl acetate. After about 1 hour, the ethyl acetate fraction was extracted and the supernatant was taken to obtain the ethyl acetate fraction. The fractionation procedure was repeated three times, after which the supernatant was concentrated under reduced pressure to give 17.3 g of ethyl acetate fraction (hereinafter referred to as " DMEA ").

2-3. From the extract of Hwangchu - Butanol Fraction  Produce

The distilled water fraction obtained in the step of obtaining ethyl ethyl acetate fraction was concentrated under reduced pressure, and then a total of 1.2 L of distilled water was added to suspend the suspension. Then, 1.2 L of n-butanol saturated with water was added to extract the fraction. After about 1 hour, the n-butanol fraction was extracted from the supernatant obtained in the n-butanol fraction. The fractionation procedure was repeated three times, after which the supernatant was concentrated under reduced pressure to obtain 41.2 g of the n-butanol fraction (hereinafter referred to as " DMBU ").

2-4. Water from the Houttuynia cordata extract Fraction  Produce

The distilled water fraction obtained in the step of obtaining the yellowing oil n-butanol fraction was concentrated under reduced pressure to obtain 14.7 g of a water fraction (hereinafter referred to as " DMWA ").

Experimental Example 1. Experimental animal blood pressure measurement experiment

In order to confirm the effect of the above-mentioned examples on the blood pressure of the experimental animals, experiments were conducted as described below (Kurtz TW, et al., Biological variability in Wistar-Kyoto rats. Implications for research the spontaneously hypertensive rat. Hypertension 10 (1): 127-31 (1987))

In this study, mature Wistar-Kyoto rats (WKR, male, 10 weeks, 300 ~ 320 g, central animal test) were used as a normal control and spontaneously hypertensive rats (SHR, male, 300 to 320 g, central animal experiment) was used.

Animals fed from the Central Animal Experiment were adapted to the rodent feeder room for one week, and normal state was observed during the adaptation period, so only healthy individuals were used for the experiment. The breeding environment was maintained at a temperature of 23 ± 3 ° C and a humidity of 50 ± 5% for 12 hours. Body weight was measured for the animals that were judged to be healthy during the refinement period, and individuals close to the average body weight were selected and subjected to group separation using the random method.

In the present study, 50 mg / kg of Hwangchu-tree ethanol extract, 50 mg / kg of n-hexane fraction and 50 mg / kg of Hwangchu-myeon ethyl acetate fraction were administered to normal control, hypertension control group, 50 mg / (50 mg / kg), and 50 mg / kg of Fusarium oxysporum fructicum fraction (50 mg / kg). The test material was tested on the assumption that the purity was 100%. Oral administration was carried out using 0.5% CMC (carboxymethylcellulose, C5678, Sigma, St. Louis, Mo., USA) immediately before administration. In the normal control and experimental control groups, 0.5% CMC was added to the water extract, the ethanol extract, the n-hexane fraction, the ethyl acetate fraction, the n-butanol fraction and the water fraction, Lt; / RTI > All test animals were fasted for 24 hours prior to autopsy.

The animals were anesthetized using Zoletil (Virbac, Carros, France) and Rompun (Bayer, Pittsburgh, Pa., USA), and the chest wall was immediately opened to expose the origin of the cardiac and major vessels. A catheter (0007760, ALZET Catheters) were inserted to measure blood pressure.

The blood pressure was normalized to 137.4 ± 5.9 mmHg in the normal control group and 211.8 ± 8.3 mmHg in the hypertensive control group. The blood pressure of the animal treated with ethyl acetate fraction was 166.7 ± 5.9 mmHg, which was the lowest, followed by 188.6 ± 4.7 mmHg in the ethanol extract. In the other experimental groups, the water extract was 198.6 ± 5.4 mmHg, the n-hexane fraction was 204.3 ± 3.9 mmHg, the n-butanol fraction was 190.3 ± 7.3 mmHg, and the water fraction was 216.8 ± 6.4 mmHg (see FIG.

Experimental Example 2. Serum Angiotensin II  ( Angiotensin II ) Concentration measurement experiment

Experiments were conducted as described below in order to confirm the effect of the samples of the above Examples on the concentration of serum angiotensin II (Hans R., et al .. Essential Hypertension: Renin and Aldosterone, Heart Attack and Stroke. N Engl J Med 286: 441-449 (1972)).

After the autopsy of Experimental Example 1, the blood was collected and centrifuged at 2,000 rpm for 20 minutes in a centrifuge (Micro 17R, Hanil, Korea) to obtain serum, and the concentration of Angiotensin II was confirmed. Serum angiotensin II (Angiotensin II) levels were measured using an Angiotensin II EIA Kit (589301, Cayman Chemical, Ann Arbor, Michigan, USA).

Angiotensin II is involved in sympathetic nervous system activity, aldosterone secretion, sodium reabsorption, moisture retention, and vasoconstriction, thereby increasing blood pressure and raising blood pressure. Therefore, blood pressure and angiotensin II are closely related and are used as an important index to evaluate blood pressure control function (Hans R., et al .. Essential Hypertension: Renin and Aldosterone, Heart Attack and Stroke. N Engl J Med 286: 441- 449 (1972)).

Angiotensin II concentration was 0.52 ± 0.18 pg / mL in the normal control group, but 3.28 ± 0.44 pg / mL in the hypertensive control group (p <0.05). The extracts of water extracts were 3.34 ± 0.29 pg / mL, ethanol extract 2.54 ± 0.54 pg / mL, n-hexane fraction 2.77 ± 0.64 pg / mL, ethyl acetate fraction 1.98 ± 0.45 pg / mL, n-butanol fraction 2.41 ± 0.39 pg / mL, and the water fraction was 3.09 0.68 pg / mL. Ethyl acetate fraction was the lowest, Ethanol extract and n-hexane fraction of the n-butanol fraction were significantly lower than those of the hypertensive control group (p <0.05) (see FIG. 3).

Experimental Example  3. Serum Angiotensin  Converting enzyme ( Angiotensin Converting Enzyme , ACE ) Concentration measurement experiment

In order to confirm the effects of the samples of the above Examples on the concentration of serum angiotensin converting enzyme (ACE), experiments were conducted as described below (Hans R., et al .. Essential Hypertension : Renin and Aldosterone, Heart Attack and Stroke. N Engl J Med 286: 441-449 (1972)).

After the autopsy of Experimental Example 1, the blood was collected and centrifuged at 2,000 rpm for 20 minutes in a centrifuge (Micro 17R, Hanil, Korea) to obtain serum, and the concentration of angiotensin converting enzyme (ACE) . Angiotensin converting enzyme was measured by enzyme-linked immunosorbent assay (ELISA) using an ACE diagnostic kit (RAB0002, Sigma Diagnostics, St. Louis, Mo., USA) and COBAS MIRA (H7587, Roche, Basel, Switzerland).

Angiotensin Converting Enzyme (ACE) is an enzyme that activates angiotensin I (Angiotensin I) with angiotensin II (Angiotensin II), which causes hypertension. Therefore, the concentration of angiotensin converting enzyme is used as an important indicator for evaluating hypertension (Hans R., et al. Essential Hypertension: Renin and Aldosterone, Heart Attack and Stroke. N Engl J Med 286: 441-449 (1972)) .

The angiotensin converting enzyme concentration, which was 177.4 ± 4 U / mL in the normal control group, was increased to 194.6 ± 7 U / mL in the hypertensive control group. Water extracts and water fractions did not show a tendency to decrease as compared with the hypertension control group. However, it was found that the ethanol extract decreased to 187.3 ± 8 U / mL, the n-hexane fraction decreased to 190.0 ± 9 U / mL, the ethyl acetate fraction decreased to 184.5 ± 7 U / mL and the n-butanol fraction decreased to 190.7 ± 6 U / (Table 1).

Effect of extracts or fractions of Hwangchulchun tree on serum angiotensin converting enzyme Group Serum angiotensin converting enzyme (ACE) concentration (U / mL) Normal control group 177.4 ± 4 Hypertension control 194.6 ± 7 Water extract 196.4 ± 6 Ethanol extract 187.3 ± 8 n-hexane fraction 190.0 ± 9 Ethyl acetate fraction 184.5 ± 7 n-butanol fraction 190.7 ± 6 Water fraction 201.7 ± 8

Experimental Example 4. Measurement of serum aldosterone concentration

Experiments were carried out as described below (Hans R., et al., Essential Hypertension: Renin and Aldosterone, Hearts) by using the method described in the literature to confirm the effect on serum aldosterone concentration of the above- Attack and Stroke N Engl J Med 286: 441-449 (1972)).

After the autopsy of Experimental Example 1, the blood was collected and centrifuged at 2,000 rpm for 20 minutes in a centrifuge (Micro 17R, Hanil, Korea) to obtain serum, and the concentration of aldosterone was confirmed. Serum aldosterone concentrations were measured using an Aldosterone EIA kit (10004377, Cayman Chemical, Ann Arbor, Michigan, USA).

The aldosterone concentration in the normal control group was 34.1 ± 22.6 pg / mL, which was 299.7 ± 54.8 pg / mL in the hypertensive control group, which was 8 times higher than that in the normal control group. On the other hand, in the test group, water extracts 250.3 ± 34.1 pg / mL, ethanol extract 219.7 ± 27.9 pg / mL, n-hexane fraction 283.1 ± 41.3 pg / mL, ethyl acetate fraction 160.5 ± 20.8 pg / mL, n-butanol fraction 193 ± 36.7 pg / mL, and the water fraction was 311.4 ± 94.3 pg / mL. Ethyl acetate fraction, followed by n-butanol fraction (p <0.05). Water extract, n-hexane fraction and water fraction were not significantly different from hypertensive controls (p <0.05) (see FIG. 4).

The preparation examples of the pharmaceutical composition containing the extract of the present invention will be described, but the present invention is not intended to be limited thereto but is specifically explained.

Preparation Example 1. Preparation of powder

DME ----------------------------------------- 300 mg

Lactose hydrate ---------------------------------- 100 mg

Talc ----------------------------------------- 10 mg

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

Formulation Example 2. Preparation of tablets

DMW ---------------------------------------- 300 mg

Corn starch --------------------------------- 100 mg

Lactose baggage --------------------------------- 100 mg

Magnesium stearate -------------------------- 2 mg

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

Formulation Example 3. Preparation of capsules

DMHE ----------------------------------------- 300 mg

Microcrystalline cellulose ------------------------------- 3 mg

Lactose hydrate ---------------------------------- 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.

Formulation Example 4. Preparation of injection

DMEA ----------------------------------------- 300 mg

Di-mannitol ------------------------------------ 180 mg

Sterile sterile distilled water for injection 2974 mg

Na ₂ HPO ₄ 12H ₂ O ----------------------------------- 26 mg

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

Formulation Example 5. Preparation of a liquid preparation

DMBU ----------------------------------------- 300 mg

Ising Party --------------------------------------- 10 g

Di-mannitol --------------------------------------- 5 g

Purified water -----------------------------------------

Each component was added to purified water in accordance with the usual liquid preparation method and dissolved, 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 adjusted to 100 ml with purified water, And sterilized to prepare a liquid preparation.

Formulation example  6. Manufacture of health food

DMWA ---------------------------------------- 1000 mg

Vitamin mixture ----------------------------------

Vitamin A Acetate --------------------------- 70 [mu] g

Vitamin E ------------------------------------- 1.0 mg

Vitamin B ₁ ------------------------------------ 0.13 mg

Vitamin B ₂ ------------------------------------- 0.15 mg

Vitamin B ₆ -------------------------------------- 0.5 mg

Vitamin B ₁₂ ------------------------------------- 0.2 [mu] g

Vitamin C ------------------------------------- 10 mg

Biotin --------------------------------------- 10 μg

Nicotinic amide ------------------------------ 1.7 mg

Folic acid ----------------------------------------- 50 μg

Calcium pantothenate ------------------------------- 0.5 mg

Inorganic mixture ---------------------------------

Ferrous sulfate ---------------------------------- 1.75 mg

Zinc oxide - 0.82 mg

Magnesium carbonate ------------------------------- 25.3 mg

Potassium phosphate monohydrate 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.

Formulation example  7. Manufacture of health drinks

DMEA ----------------------------------------- 300 mg

Vitamin C --------------------------------------- 15 g

Vitamin E (powder) -------------------------------- 100 g

Lactic Acid Iron -------------------------------------- 19.75 g

Zinc oxide -------------------------------------- 3.5 g

Nicotinic acid amide -------------------------------- 3.5 g

Vitamin A -------------------------------------- 0.2 g

Vitamin B ₁ ------------------------------------- 0.25 g

Vitamin B ₂ -------------------------------------- 0.3 g

Water ---------------------------------------------- QUANTITY

The above components were mixed according to a conventional health drink manufacturing method, and the mixture was stirred and heated at 85 ° C for about 1 hour. The solution was filtered to obtain a sterilized 2-liter container, which was sealed and refrigerated It is used in the production of the health beverage composition of the present 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 (9)

A pharmaceutical composition for the prevention and treatment of hypertension, comprising an extract of Aspergillus oryzae as an active ingredient. The method according to claim 1,
Wherein the extract is a crude extract, a polar solvent-soluble extract or a non-polar solvent-soluble extract. 3. The method of claim 2,
Wherein the crude extract is an extract which is soluble in a solvent selected from water containing purified water, a lower alcohol having 1 to 4 carbon atoms such as methanol, ethanol, butanol or a mixed solvent thereof. 3. The method of claim 2,
Wherein the non-polar solvent-soluble extract fraction comprises extract fractions obtained by extracting the crude extract of claim 3 in a non-polar solvent obtained by purifying only the extract soluble in hexane, methylene chloride, chloroform, or ethyl acetate solvent. 3. The method of claim 2,
Wherein the polar solvent-soluble extract comprises an extract fraction obtained by removing the non-polar solvent-soluble fractions from the crude extract of claim 3 and using the remaining fraction in a solvent selected from water, methanol, butanol or a mixed solvent thereof. The method according to claim 1,
Wherein the hypertension defined above is essential hypertension, or secondary hypertension. The method according to claim 1,
Wherein said woodwort comprises whole parts of branches, leaves, roots, and rounds. A health functional food for prevention and improvement of hypertension containing extract of Hwangchil tree as an active ingredient. 9. The method of claim 8,
The health functional food is a health functional food in the form of a food, a powder, a granule, a tablet, a capsule, a syrup, a beverage, a gum, a tea, a vitamin complex, or a health functional food.

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