KR100732886B1 - Composition having antihypertensive effect comprising extract of moutan cortex radicis or active compounds isolated therefrom - Google Patents

Abstract

The present invention is an antihypertensive composition containing Moutan Cortex Radicis extract, oxypaeoniflorin, paeoniflorin, methylpaeoniflorin or paonidanin as an active ingredient. It is about. Since 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 food additive as well as a pharmaceutical composition for the prevention and treatment of various cardiovascular diseases caused by complications of hypertension and hypertension.

Description

Composition for lowering blood pressure, comprising a extract of neck peel or an active ingredient separated therefrom {COMPOSITION HAVING ANTIHYPERTENSIVE EFFECT COMPRISING EXTRACT OF MOUTAN CORTEX RADICIS OR ACTIVE COMPOUNDS ISOLATED THEREFROM}

1 is a result of measuring the vascular smooth muscle relaxation effect by administering the extract of the neck of the present invention after contraction by treating phenylephrine (PE), a vasoconstrictor, to the thoracic aortic smooth muscle extracted from rats,

Fig. 2 is a contraction of phenylephrine, a vasoconstrictor, to aortic smooth muscles extracted from the chest of rats, followed by contraction. One result.

The present invention is a blood pressure lowering drug containing Moutan Cortex Radicis extract, oxypaeoniflorin, paeoniflorin, methylpaeoniflorin or paonidanin as an active ingredient. To a composition.

Blood pressure refers to the pressure of blood flow through the vasculature, 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 more. Hypertension is divided into essential hypertension and secondary hypertension. Essential hypertension is a disease caused by lifestyle, including family history, and its exact cause is not known yet. Secondary hypertension, on the other hand, is a disease temporarily caused by other diseases, and is cured naturally when the causative disease is cured. The classification of hypertension is different depending on the cause of the sympathetic nervous system, cell membrane dysfunction, renal water and Na excretion, secretion of hypotensive agents such as PGE ₂ , PGI ₂ , ANP and EDRF. Lowering or abnormality of hypertension control function such as catecholamines, renin- angiotensin system (renin-angiotensin) is the cause. Therefore, the 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 a cure by treatment, it has the disadvantage of taking a drug for a lifetime while starting hypertension treatment. Therefore, there is an urgent need for the development of new therapeutic agents that can mitigate side effects due to tissue specificity or resistance.

Meanwhile, Moutan Cortex Radicis is a herb that refers to the root of Paeonia moutan Sims belonging to the Paeoniaceae family. It is used for traumatic inflammation such as medicine, back pain, bruises, abdominal purulent diseases such as appendicitis, and inflammatory diseases. Recent studies on bark skin have been reported on antimutagenic, anti-inflammatory, and antioxidant activities of bark skin, and the main components of the bark skin are paononoside, paeonolide, and pheonol. Paeonol and the like are well known, and phonosides are readily degraded during storage to produce sugars and pheonols. In addition, the bark skin is paeoniflorin (paeoniflorin), oxypaeoniflorin, benzoylpaeoniflorin (benzoylpaeoniflorin), paeonolide tannin, procyanidine B1 (procyanidin B1), benzoyloxyphenoni Florin (benzoyloxypaeoniflorin), paeonin (paeonin), paeonidanin (paeonidanin) and gallic acid (gallic acid) is contained. Palonol of the woody bark component has an antimicrobial effect of inhibiting the growth of Escherichia coli, Staphylococcus aureus, Streptococcus, Bacillus subtilis, etc., benzoylphaniflorin, benzoyloxyphaniflorin and the like has a histamine free inhibitory activity in mast cells, Phonolide tannins have been reported to have antiviral action.

Therefore, the present inventors examined the vascular smooth muscle relaxation effect of these extracts in various herbal medicines including pelvic dermis, and confirmed that the pelvic extract exhibits a blood pressure lowering effect through a powerful vascular smooth muscle relaxation effect, and from this the blood pressure lowering effect The present invention was completed by separating and purifying the active substances.

Accordingly, it is an object of the present invention to provide an antihypertensive agent comprising an extract of bark skin useful for the prevention and treatment of hypertension and cardiovascular diseases caused therefrom.

It is also an object of the present invention to provide a food having a blood pressure lowering effect using the extract of the bark of the neck.

In order to achieve the above object, the present invention comprises an effective amount of the extract of neck peel, oxyphaoniflorin, pheoniflorin, methylphenoniflorin or peonidin with a pharmaceutically acceptable carrier, vascular smooth muscle relaxation It provides a composition exhibiting a blood pressure lowering effect through the action.

Hereinafter, the present invention will be described in detail.

The composition according to the present invention is that the extract containing the bark skin extract having a blood pressure lowering effect through vascular smooth muscle relaxation, oxyphaoniflorin, peoniflorin, methylpaoniflorin or peonidanin separated and purified therefrom as an active ingredient It features.

First, the extract of the bark of the present invention can be prepared by solvent extraction of the bark or dried product thereof.

The bark extract of the present invention is added to the organic solvent of 2 to 200 times, preferably 10 to 30 times the volume of the dried dry bark, and 1 to 20 days at 10 to 30 ℃, preferably 3 to 7 days Extraction, cooling, filtration and concentration under reduced pressure. At this time, the extraction solvent may be used methanol, methanol aqueous solution, ethanol, ethanol aqueous solution, butanol, dichloromethane, ethyl acetate or a mixture thereof, 80 to 100% aqueous methanol solution is preferred. Methanol extract extracted with methanol can be re-extracted with a solvent such as butanol, dichloromethane or ethyl acetate. Preferably re-extracted with ethyl acetate. Specifically, in a preferred embodiment of the present invention, the bark or dried product thereof is cooled for 7 days using 100% methanol aqueous solution, filtered, and the filtrate is concentrated under reduced pressure to obtain a methanol extract, and the methanol extract is suspended in distilled water, followed by the same amount. The water layer extracted by dichloromethane was extracted with the same amount of ethyl acetate and concentrated under reduced pressure to obtain a bark extract. Methanol and ethyl acetate extracts of the neck bark showed a blood pressure lowering effect through vascular relaxation. In particular, the vasorelaxant effect of ethyl acetate extract of the bark skin was excellent (see Table 1 and Figure 1 ).

In the present invention, chromatography is performed to separate and purify the active ingredient from the ethyl acetate extract of the bark skin, which has a blood pressure-lowering effect through vascular relaxation. The chromatography is preferably performed 1-2 times using reverse phase silica gel column chromatography. Methanol can be used as a mobile phase. At this time, the eluted fraction by gradient elution to sequentially raise the methanol concentration to 0, 20, 40, 60, 80 and 100%, and to obtain the active fraction by measuring the blood pressure drop effect of the collected fractions Can be.

To the re-purified by reverse phase column chromatography The active fractions showing a blood pressure lowering effect of sludge oxy L of formula Florin (oxypaeoniflorin), methyl L sludge Florin (methylpaeoniflorin) and the formula of the formula (2) L sludge Florin (paeoniflorin), formula (3) of the 4 , paeonidanin is obtained.

The compounds exhibited an excellent blood pressure lowering effect through vascular smooth muscle relaxation in the contraction and relaxation experiments on the extracted blood vessels of rats (see Table 1 and FIG. 1 ).

Barberry extract according to the present invention, the composition for lowering blood pressure containing oxyphaoniflorin, peonyflorin, methylphaoniflorin or peonidanin isolated and purified therefrom as an active ingredient may be a pharmaceutical composition or a food composition.

It is preferable that the extract of neck bark included in the pharmaceutical composition of the present invention is purified through column chromatography, but an extract obtained by simply solvent extraction may also be included. In addition, oxyphaoniflorin represented by the above formulas (1) to ( 4) , pheoniflorin, methylphenoniflorin and peonidanin can be isolated, purified or chemically synthesized from the dermis extract.

The pharmaceutical composition according to the invention is characterized in that it is used for the prevention or treatment of hypertension or hypertension complications. Hypertension refers to a condition in which the systolic blood pressure, diastolic blood pressure or average arterial pressure is continuously maintained higher than normal in a stable state, and in general, when the systolic blood pressure is continuously maintained at 120 mmHg or more and the diastolic blood pressure is 80 mmHg or more. Say. Hypertension complications refer to diseases caused by abnormally elevated blood pressure, including, but not limited to, coronary artery disease, cerebrovascular disease, peripheral vascular disease, aortic disease, renal dysfunction, and heart failure. And vision disorders. Examples of the coronary artery disease include angina and myocardial infarction, and examples of cerebrovascular diseases include stroke, cerebral hemorrhage, and cerebral infarction. In addition, the pharmaceutical composition according to the present invention can be administered individually or in combination with other types of blood pressure lowering agents.

Peel extract, oxypaoniflorin, peonyflorin, methylpaoniflorin or peonidanin isolated and purified therefrom may be mixed with a suitable pharmaceutically acceptable carrier or excipient or diluted with a diluent according to conventional methods. Pharmaceutical compositions having the function 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, undecided Vaginal 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 invention can 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 formulations 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, the bark extract is in the range of 10 to 100 mg / kg body weight, preferably 10 to 30 mg / kg body weight, oxyphaniflorin, Paoniflorin, methylphenoniflorin and peonidanin are each in the range of 1 to 30 mg / kg body weight, preferably 1 to 10 mg / kg body weight, and can be administered once or in several doses. However, it should be understood that 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 may be determined in any respect to the invention It does not limit the scope of.

In addition, in the present invention, an effective amount of the extract of bark skin, including oxyphaoniflorin, pheoniflorin, methylphaoniflorin or peonidanin, separated and purified therefrom, the health promotion that can prevent or alleviate hypertension and hypertension complications It provides a food composition for. In order to achieve the above effects, as a food to which the extract of the bark of the present invention, oxyphaoniflorin, peonyflorin, methylphaoniflorin or peonidin, separated and purified therefrom, may be added, for example, various foods, Beverages, snacks, sweets, gums, ice creams, tea bags, instant teas, granules, flavorings, vitamin complexes, and other health supplements, but are not limited thereto.

Bark extract of the present invention, oxyphaoniflorin, peonyflorin, methylphaoniflorin or peonidanin separated and purified therefrom is added to the raw material during food production or properly mixed in the cooked food for health promotion as described above It is possible to prepare a food or drink, in which case the content of the bark extract, oxyphaoniflorin, pheoniflorin, methylphaoniflorin or peonidin in the finally prepared food or drink is 0.01 To 30% by weight.

The pharmaceutical composition or health promoting food or beverage of the present invention may further include other medicinal herbs or extracts thereof which are pharmaceutically acceptable to enhance or supplement the desired effect, such herbal medicines include rhubarb, triticale, ear The woowoo, baekbaekpi, or soft meat, etc. can be illustrated. 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 by the following Preparation Examples and Examples.

The following Preparation Examples and Examples are only for illustrating the present invention, but the scope of the present invention is not limited thereto.

Example 1 Preparation of Bark Bark Extract and Separation of Active Ingredients

6 kg of dried bark was cooled in 20 L of methanol for 1 week, filtered and the filtrate was concentrated under reduced pressure to obtain 650 g of methanol extract. The methanol extract was suspended in 20 L of distilled water and extracted with the same amount of dichloromethane (CH ₂ Cl ₂ ). The separated water layer was extracted again with the same amount of ethyl acetate (ethylacetate, EtOAc), and the extract was concentrated under reduced pressure to obtain 117 g of ethyl acetate (EtOAc) extract, and the remaining water layer was freeze-dried.

10 g of the ethyl acetate (EtOAc) extract was a methanol / distilled water mixed solution as a mobile phase and flowed at a flow rate of 3 ml / hour while increasing the concentration of methanol sequentially from 0% to 100% of a gradient elution method (gradient elution). It was analyzed by reverse phase (RP-18) column chromatography. This gave a total of five fractions (Fr.1 to Fr.5). The first, second and fifth fractions of these were purified by RP-18 reverse phase chromatography (mobile phase: 0 to 100% MeOH), respectively. As a result, 30 mg of oxypaeoniflorin was obtained from the first fraction. From the second fraction, 850 mg of paeoniflorin, and from the fifth fraction 90 mg of methylpaeoniflorin and 90 mg of paonidanin Separated.

Oxypheniflorin

¹ H-NMR (DMSO-d _6, 300 MHz) 0.99 (3H, s, H-10), 1.63 (1H, d, J = 12.4, H-7a), 1.78 (1H, d, J = 10.4HZ, Ha -3), 2.04 (1H, d, J = 12.4 Hz, Hb-7), 5.28 (1H, s, H-9), 6.85 (2H, d, J = 8.0 Hz, H-3 ", 5") , 7.83 (2H, d, J = 8.0 Hz, H-2 ", 6")

¹³ C-NMR (DMSO-d _6, 125 MHz) 19.1 (C-10), 22.1 (C-7), 42.3 (C-5), 43.6 (C-3), 59.8 (C-8), 61.2 (C -6 '), 70.1 (C-4'), 70.2 (C-6), 73.4 (C-2 '), 76.9 (C-3', 5 '), 84.9 (C-2), 87.5 (C- 1), 98.6 (C-1 '), 100.1 (C-9), 104.7 (C-4), 115.3 (C-3 ", 5"), 120.2 (C-1 "), 131.5 (C-6" ), 131.6 (C-2 "), 162.1 (C-4"), 165.6 (C = O)

Paoniflorin

¹ H-NMR (DMSO-d ₆ , 300 MHz) 1.24 (3H, s, H-10), 1.64 (1H, d, J = 12.3 Hz, Ha-7), 1.8 (1H, d, J = 10.4 Hz) , 2.0 (1H, d, J = 12.3 Hz, Hb-7), 4.37 to 5.07 (7H), 5.32 (1H, s, H-9) 7.5 (2H, d, J = 7.7 Hz, H-3, 5 ), 7.6 (1H, t, J = 7.2 Hz, H-4), 7.9 (2H, d, J = 7.2 Hz, H-2,6)

¹³ C-NMR (DMSO-d ₆ , 125 MHz) 19.6 (C-10), 23.4 (C-6), 43.9 (C-5), 44.5 (C-3), 61.7 (C-8), 62.8 (C -6 '), 71.7 (C-4'), 72.2 (C-7), 75.0 (C-2 '), 77.9 (C-3'), 78.0 (C-5 '), 87.2 (C-2) , 89.3 (C-1), 100.1 (C-1 '), 102.3 (C-9), 106.4 (C-4), 129.6 (C-3 ", 5"), 130.7 (C-2 ", 6" ), 131.1 (C-1 "), 134.2 (C-4"), 168.0 (C = O)

Methylpheoniflorin

¹ H-NMR (DMSO-d _6, 300 MHz) 1.39 (3H, s, H-10), 1.94 (1H, d, J = 11.0 Hz, Hb-3), 1.96 (1H, d, J = 1.7, Hb -7), 2.14 (1H, d, J = 12.6 Hz, Ha-3), 2.49 (1H, dd, J = 7.1, 11.0 Hz, Ha-7), 2.77 (1H, dd, J = 1.7, 4.4 Hz , H-5) 3.26 (3H, m, H-2 ', 4', 5 '), 3.31 (1H, s, H-3'), 3.37 (3H, s, -OMe), 3.63 (1H, m , Ha-6 '), 3.85 (1H, dd, J = 1.3, 12.0 Hz, Hb-6'), 4.53 (1H, d, J = 7.7 Hz, H-1 '), 4.76 (2H, s, Hb -8), 5.47 (1H, s, H-9), 7.49 (2H, t, J = 8.3 Hz, H-3 ", 5"), 7.60 (1H, tt, J = 1.3, 7.5 Hz, H- 4 "), 8.04 (2H, dd, J = 1.5, 8.3 Hz, H-2", 6 ")

¹³ C-NMR (CD ₃ OD ₃ , 125MHZ) 18.2 (C-10), 22.0 (C-7), 39.6 (C-5), 40.8 (C-3), 50.1 (-OMe), 60.3 (C- 8), 61.4 (C-6 '), 70.4 (C-4,6'), 73.6 (C-2 '), 76.6 (C-3,5'), 85.8 (C-2), 87.8 (C- 1), 98.7 (C-1 '), 101.1 (C-9), 108.1 (C-4), 128.3 (C-3 ", 5"), 129.2 (C-2 ", 6"), 129.7 (C -1 "), 133.1 (C-4"), 166.6 (C = O)

Paoninin

¹ H-NMR (DMSO-d _6, 300 MHz) 1.32 (3H, s, H-10), 2.09 (1H, d, J = 10.8 Hz, H-7a), 2.34 (1H, d, J = 18 Hz, H -7b), 3.26 (3H, s, -OMe), 4.44 (1H, d, J = 7.6 Hz, H-1 '), 4.59 (2H, s, H-8), 5.02 (1H, s, H- 9), 7.54 (2H, t, J = 7.4 Hz, H-3 ", 5"), 7.66 (1H, t, J = 7.3 Hz, H-4 "), 7.95 (2H, d, J = 7.1 Hz , H-2 ", 6")

¹³ C-NMR (DMSO-d ₆ , 125 MHz) 19.3 (C-10), 26.1 (C-7), 47.0 (C-5), 48.3 (C-3), 54.4 (-OMe), 61.5 (C- 6), 62.5 (C-8), 63.7 (C-6 '), 70.3 (C-4'), 73.6 (C-2 '), 76.6 (C-3', 5 '), 86.1 (C-2 ), 87.2 (C-1), 98.5 (C-1 '), 106.2 (C-9), 128.2 (C-3 ", 5"), 129.2 (C-2 ", 6"), 129.7 (C- 1 "), 133.0 (C-4"), 166.1 (C-7 "), 208.2 (C-4)

Example 2 Determination of Extraction Vascular Relaxation Effects of Extracts from Mori Bark and Active Ingredients

Methanol and ethyl acetate extract of the bark skin according to the present invention, whether or not the hypotensive effect of oxyphenoniflorin, pheoniflorin, methylphenoniflorin and peonidanin isolated and purified from the vascular smooth muscle The protective effect of the vasoconstrictor was investigated.

Sprague-Dawley (SD, male) rats (Orient, South Korea) at least 2 in a clean animal room with automatic adjustment of contrast at constant temperature (22.5 ± 1 ℃), humidity (55 ± 5%) and 12 hour intervals. It was used for the experiment after stabilizing for more than a week. 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 lengths of 2-3 mm (Krebs-Henseleit or Krebs' bicarbonate buffer: NaCl 118.0, KCl 4.7 mM, CaCl ₂ 2.5, MgSO ₄ 1.2, KH ₂ PO ₄ 1.2, NaHCO ₃ 25.0, glucose 11.0 mM, Junsei, Japan, hereinafter referred to as "KH buffer") suspended in a tissue chamber (tissue chamber). At this time, the temperature in the chamber was maintained at 37 ℃, saturated with O ₂ / CO ₂ mixed gas to maintain a pH of 7.4. Equilibration was carried out at 2 g of initial tension for 1 hour and exchanged with fresh KH buffer at 15 minute intervals. Vasoconstriction / relaxation was recorded on a chart recorder (chart recorder, Multicorder MC 6625, Hugo Sachs, Germany) via a force displacement transducer (Grass FT03, Grass, USA).

To adapt the bleeding vessels in the tissue chamber, it was shrunk with 0.3 μM of phenylephrine (phenylephrine, Sigma-Aldrich Co., St. Louis, Mo. USA) and washed three times over 45 minutes with KH buffer. It was. The bleeding blood vessel was contracted again with phenylephrine to reach a stable state, and then 1 μM acetylcholine chloride (acetylcholine chloride, Sigma-Aldrich Co., St. Louis, Mo. USA) was added to completely relax the blood vessel. It was confirmed that the endothelial was not damaged. The sample used in this experiment was dissolved in DMSO (dimethylsulfoxide) and diluted with K-H buffer solution. The highest concentration of DMSO was 0.03%. 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 ㎍ / ㎖) to measure the degree of relaxation of the vessels. At this time, the results of the experiment was expressed as a degree of relaxation on the basis of the contraction state by phenylephrine in%, and the EC ₅₀ value (concentration to relax 50%) through the linear regression analysis to obtain the shown in Table 1 below.

As described above, after contraction by administering phenylephrine to the aortic blood vessels extracted from SD rats, the methanol extract of the present invention was administered by concentration, and the methanol extract of the epidermis was concentrated by the vasoconstrictor. It was found to be dependent on relaxation. Meanwhile, each solvent fraction, that is, dichloromethane fraction, obtained by fractionally extracting methanol extract from methanol, dichloromethane (CH ₂ Cl ₂ ), ethyl acetate (EtOAc) and water (H ₂ O) as in Example 1 Vasorelaxation effect was examined by the same method using the ethyl acetate fraction and the water fraction as sample specimens. The ethylacetate fraction showed a relatively superior vasorelaxant effect compared to the dichloromethane fraction and the water fraction, and EC ₅₀ was 6.8 ㎍. It was measured in / ml ( FIG. 1 ).

In addition, as a result of investigating the vasorelaxant effect of oxyphaoniflorin, pheoniflorin, pheonidanin and methylphaoniflorin purified through column chromatography from the ethyl acetate fraction, these active substances were all excellent It showed a vasorelaxant effect. EC ₅₀ of each compound is summarized in Table 1 and FIG. 2 .

From the above results, it was confirmed that the extract of the bark of the present invention, oxyphaoniflorin, pheoniflorin, peonidanin and methylphaoniflorin according to the present invention has an excellent blood pressure lowering effect through vascular relaxation. It was.

The extract of the bark of the present invention or the active ingredient isolated and purified therefrom may be in the form of preparations such as powders, tablets, capsules, injections, liquids and the like according to the methods commonly used pharmaceutically or in combination with excipients used alone or pharmaceutically. Can be formulated and used.

Formulation examples are illustrated below.

Production Example 1 Powder

Dry bark extract or active ingredient isolated and purified from it 2 g

1 g lactose

The above ingredients are mixed and filled in an airtight cloth to prepare a powder.

Preparation Example 2 Tablet

Dry extract of dried bark or 100 mg of active ingredient isolated and purified from it

Corn starch 100 mg

Lactose 100 mg

2 mg magnesium stearate

After mixing the above components and tableting according to the conventional tablet manufacturing method to produce a tablet.

Preparation Example 3 Capsule

Dry extract of dried bark or 100 mg of active ingredient isolated and purified from it

Corn starch 100 mg

Lactose 100 mg

2 mg magnesium stearate

After mixing the above components to fill a gelatin capsule in accordance with the conventional capsule preparation method to prepare a capsule.

Production Example 4 Injection

Dry extract of dried bark or 100 mg of active ingredient isolated and purified from it

Suitable amount of distilled water for injection

pH adjuster

According to a conventional injection preparation method, the active ingredient is dissolved in distilled water for injection, the pH is adjusted to about 7.5, and the whole is filled with 2 ml of ampoule with injection distilled water and sterilized to prepare an injection.

In addition, health foods and alcoholic beverages are prepared in the following manner.

<Manufacture example 5> 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 dried bark extract of the present invention was decompressed and concentrated in a vacuum concentrator, dried by spraying and drying with a hot air dryer, and then pulverized with a particle size of 60 mesh using a grinder to obtain an extract dry powder.

Granules were prepared by combining the dry powders of grains, seeds and bark 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,

Dry bark extract dry powder 3% by weight, ganoderma lucidum 0.5% by weight, egg yolk 0.5% by weight

Preparation Example 6 Chewing Gum

Chewing gum was prepared in a conventional manner by combining 20% by weight of the 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 the extract of the bark of the present invention.

Production Example 7 Candy

Candy was prepared by the conventional method by combining 60% by weight of sugar, 39.8% by weight of starch syrup, 0.1% by weight of fragrance, and 0.1% by weight of the bark extract of the present invention.

Production Example 8 Biscuits

Force 1st class 25.59 wt%, 1st class gravity 22.22 wt%, white sugar 4.80 wt%, salt 0.73 wt%, glucose 0.78 wt%, palm shortening 11.78 wt%, ammonium 1.54 wt%, sodium bicarbonate 0.17 wt%, sodium bisulfite 0.16 wt %, Rice flour 1.45 wt%, Vitamin B₁0.0001 wt%, Vitamin B20.0001 wt%, Milk flavor 0.04 wt%, Water 20.6998 wt%, Whole milk powder 1.16 wt%, Substitute milk powder 0.29 wt%, Calcium phosphate 0.03 wt% , 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 neck peel.

<Manufacture example 9> 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 1% by weight of the extract of bark of the neck was prepared in a conventional manner for a healthy drink.

Preparation Example 10 Health Supplement

55% by weight of spirulina, 10% by weight of guar gum enzyme digestion, 0.01% by weight of vitamin B₁ hydrochloride, 0.01% by weight of vitamin B6 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 blended with 10% by weight of the extract of the bark of the present invention to prepare a tablet-type health supplement food in a conventional manner

As described above, the composition containing the extract of neck peel according to the present invention, isolated and purified therefrom oxyphaoniflorin, pheoniflorin, pheonidanin and methylphenoniflorin as an active ingredient to relax the smooth muscle of the blood vessels Because of the excellent blood pressure lowering effect, it can be useful for the prevention and treatment of hypertension, as well as 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 (9)

A pharmaceutical composition for lowering blood pressure, which contains a compound selected from the group consisting of methylpaeoniflorin, paeonidanin, and mixtures thereof as an active ingredient. delete The method of claim 1, A pharmaceutical composition, wherein the compound is separated and purified by fractionating the extract of neck peel by reverse phase column chromatography. The method of claim 1, A pharmaceutical composition, characterized in that the pharmaceutical composition is used for the prevention or treatment of hypertension, coronary artery disease, cerebrovascular disease, peripheral vascular disease, aortic disease, renal dysfunction, heart failure or vision disorder. A health promoting food having an effect of inhibiting blood pressure increase, containing a compound selected from the group consisting of methylpaeoniflorin, paeonidanin, and mixtures thereof as an active ingredient. The method of claim 5, Health promoting food, characterized in that in the form of a drink. delete delete delete

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