KR20140146312A - A composition containing extract of saururi herba for the treatment of heart failure - Google Patents

Abstract

The present invention relates to a composition for preventing, alleviating or treating heart failure including extracts of Saururi herba as an active ingredient, which has effects of contracting heart muscle while increasing pulse pressure by 8-220% and stroke volume by 25-220% with respect to the pulse pressure and the stroke volume when the extracts of Saururi herba are not treated. According to the present invention, the composition has effects of contracting heart muscle when treated with diltiazem or nifedifine, which is an inhibitor of L-type Ca^2+ channel.

Description

TECHNICAL FIELD [0001] The present invention relates to a composition for preventing, ameliorating or treating heart failure, comprising an extract of Saururus chinensis as an active ingredient.

The present invention relates to a composition for preventing, ameliorating or treating heart failure, which comprises Saururus chinensis extract as an active ingredient. The composition comprises 8 ~ 220% pulse pressure and 25 stroke volume Up to 220%, and has the ability to contract myocardium.

The composition according to the present invention has an effect of contraction of the myocardium even when it is used in combination with nifedifine or diltiazem which is an L-type Ca ^{2 +} channel channel inhibitor.

The composition according to the present invention has a technical characteristic that the concentration is 10 < ^-3 > g / ml on the basis of the rabbit atrial rhythm perfusion model.

The heart is a muscular circulation organ with 2/3 on the left side and 1/3 on the right side based on the sternum. Its main function is to pump the oxygenated and nutrient-bound blood to each part of the body, (atrial natriuretic peptide, ANP).

The heart is largely divided into a left part and a right part. There are two atria and two ventricles on the right and left, respectively, and there is a valve between each part. The left part plays a role of fresh blood containing oxygen and nutrients, and the right part circulates the organs and circulates the waste containing carbon dioxide into the lungs to circulate the oxygen to the lungs. The heart muscle contracts about 60 to 80 times per minute for blood circulation.

Heart failure refers to a group of diseases caused by structural or functional abnormalities of the heart that cause the heart to squeeze out blood or reduce the relaxation function it receives and fail to properly supply the blood needed for each tissue in the body. Causes of heart failure include cardiovascular disease, heart muscle disease, long-lasting cardiac valvular disease, cardiac malformations and hypertension.

The pathophysiological mechanism of heart failure is a combination of left ventricular dysfunction, decreased exercise tolerance, swelling and congestion associated with body fluid, ventricular arrhythmia, stimulation of the neuroendocrine system, ventricular hypertrophy and remodeling, and vasoconstriction. Is the cause of myocardial contractility.

Therapeutic drugs for heart failure include dobutamine, digitoxin, strophanthin, and ouabain, which activate cAMP by activating the membrane-binding enzyme AC to induce hyperactivity of myocardial contractility. Cardiac glycosides, phosphodiesterase inhibitors, and antihypertensive agents.

These medications can cause side effects when taken over a long period of time. For example, cardiac glycosides, which have been used as the basis of heart failure medication, have a great advantage of rapidly improving clinical symptoms and hemodynamic stability in hemodynamically unstable patients And there are limitations in its use due to increased side effects and increased mortality associated with arrhythmia, myocardial ischemia, and increased myocardial oxygen consumption.

Therefore, the Applicant has found a composition which can prevent, ameliorate or treat diseases caused by dysfunction of the body fluid and cardiovascular homeostatic disorder and myocardial contraction and relaxation without any adverse effect using a substance derived from natural origin.

Hereinafter, Saururus chinensis, a natural material used in the present invention, will be briefly described.

Saururi Herba seu Rhizoma is a perennial herb Saururus belonging to Saururaceae, chinensis ) is a root and outpost in our country. It grows in Jeju Island and is cultivated in various places. It is collected in July-August.

The stem is cylindrical and 50 to 80 cm long. The surface is yellowish white with vertical wrinkles. Leaves are 5 ~ 15 cm long and 3 ~ 8 cm wide with sharp ends and flat edges. Leaves contain quercetin, quercitrin, isoquercitrin, quercetin-3-l-arabinoside, and the like.

The main component of the essential oil contained in the outpost is methyl-n-nonylketone.

In the prior art related to the present invention, Korean Patent Laid-Open Publication No. 10-2006-0037066 discloses a composition for prevention and treatment of a cardiovascular system disease comprising glycerol compound extracted from Saururus chinensis as an active ingredient.

The prior art does not describe the efficacy of increasing myocardial contractility.

The object of the present invention is to provide a composition for preventing, ameliorating or treating heart failure, which has the effect of increasing the pulse pressure by 8 to 220% and the amount of atrial pericardium by 25 to 220% .

Object of the present invention is to provide an L- type Ca ^{2 +} channel inhibitor nifedipine or diltiazem treatment composition, prevention, improvement or treatment of heart failure to retain the efficacy of contraction of the myocardium after.

It is an object of the present invention to provide a composition for preventing, ameliorating or treating heart failure, which contains 10 ^-3 g / ml of Saururus chinensis extract on the basis of the rabbit atrial rhythm perfusion model.

In order to achieve the above object, the present invention provides a method for preventing, ameliorating or treating heart failure, which has the effect of increasing the pulse pressure by 8 to 220% and the amount of atrial ejection by 25 to 220% To solve the technical problem.

The present invention to solve the L- type Ca ^{2 +} channel inhibitor nifedipine or diltiazem process aspect by providing a composition for the prophylaxis, improvement or treatment of heart failure to retain the efficacy of contraction of the myocardium after.

The present invention also aims at solving the technical problem by providing a composition for preventing, ameliorating or treating heart failure, which contains ^10-3 g / ml of Saururus chinensis extract on the basis of rabbit atrial pumping flow model.

In order to use the present invention as a pharmaceutical composition, it may be prepared by a known method in the pharmaceutical field, and may be mixed with the carrier itself, a pharmaceutically acceptable carrier, excipient, diluent or the like to prepare a powder, granule, Or injections, and the like. They may also be administered orally or parenterally.

The effective throughput of the composition according to the present invention may be appropriately selected depending on the degree of absorption of the active ingredient in the body, the rate of water activation and excretion, the age, sex and condition of the patient, severity of the disease to be treated,

Formulations such as pills, granules, beverages, tablets, capsules and the like may be prepared using the composition according to the present invention, and in this case, a treatment agent may be added to prepare each formulation.

The composition according to the present invention can be provided as a food composition, and each composition is prepared and provided as a health functional food using a foodstuff acceptable processing agent. The health functional food using the composition according to the present invention may be provided in various forms such as functional beverage, health supplement, tea, confectionery, and the like.

The composition according to the present invention has an effect of shrinking myocardial muscle by increasing pulse pressure by 8 to 220% and stroke volume by 25 to 220% on the basis of untreated Saururus chinensis extract.

The composition according to the present invention has an effect of contraction of the myocardium even when it is used in combination with nifedipine or diltiazem, which is an L-type Ca ^{2 +} channel channel inhibitor.

The composition according to the present invention has a specific efficacy at a concentration of 10 ^-3 g / ml based on rabbit atrial perfusion based on the concentration of the Saururus chinensis extract contained therein.

FIG. 1 is a view showing a design diagram at the time of manufacturing the atrial ventricular perfusion model.
FIG. 2 is a graph showing the results of measurement of the pulse pressure and the amount of one-time atrial ejection when the Saururus chinensis extract was treated at 10 ^-3 g / ml.
FIG. 3 is a graph showing the results of measurement of the pulse pressure and the amount of one-shot atrial discharge when the Saururus chinensis extract was treated at 10 ^-4 g / ml.
FIG. 4 is a graph comparing the results of measuring the pulse pressure and the amount of one-time atrial ejection when the concentration of Saururus chinensis extract was changed to 10 ^-3 g / ml and 10 ^-4 g / ml.
FIG. 5 is a graph showing the results of measurement of changes in pulse pressure and one-time ventricular ejection when nifedipine alone was treated and when 10 ^-3 g / ml of Saururus chinense extract and nifedipine were coadministered.
FIG. 6 is a graph showing the results of measurement of changes in pulse pressure and one-time ventricular ejection when diltiazem is administered alone and when ^10-3 g / ml of Saururus chinense extract and diltiazem are coadministered.

The terms and words used in the present specification and claims should not be construed as limited to ordinary or dictionary terms and the inventor may properly define the concept of the term in order to best describe its invention It should be construed as meaning and concept consistent with the technical idea of the present invention.

Therefore, the embodiments described in the present specification and the configurations shown in the drawings are merely the most preferred embodiments of the present invention and are not intended to represent all of the technical ideas of the present invention. Therefore, various equivalents It should be understood that water and variations may be present.

Example  1. A composition for preventing, ameliorating or treating heart failure containing Saururus chinensis extract as an active ingredient

Saururi Herba seu Rhizoma is a perennial herb Saururus belonging to Saururaceae, chinensis ) is the root and outpost.

The roots and / or outpones of Saururus chinense are extracted to prepare a composition for preventing, ameliorating or treating heart failure containing Saururus chinense extract as an active ingredient.

Various extraction methods such as a solvent extraction method, a steam distillation method, a carbon dioxide supercritical extraction method, a steam distillation method, a microwave process extraction method, and a percolation extraction method can be used for the extraction of Saururus chinensis. Preferably, a solvent extraction method is used. The extraction time may also vary.

A variety of solvents may also be used as the extraction solvent. Extractable solvents include water, ethanol, methanol, fatty oils, glycerin, mayo, flouroprene glycol, ether, chloroform, petroleum ether, hexane, benzene, methylene chloride, ethyl acetate, acetone, butanol and isopropanol. Preferably, water is used as the extraction solvent.

Depending on the design conditions, filtration, concentration, reflux extraction, etc. may be added before and after the extraction.

Various methods such as evaporation, concentration and drying can be used for the concentration method. Various drying methods such as a positive drying method, a negative drying method, a freeze drying method, a hot air drying method and the like can be used for the drying method.

Here, the concentration of Saururus chinensis extract is 10 ^-3 g / ml, preferably within a range of ± 20%, that is, in a concentration range of 0.8 × 10 ^-3 to 1.2 × 10 ^-3 g / ml ≪ / RTI > And may be selected within a concentration range that is not cytotoxic at a wide range of 10 ^-4 g / ml.

Preferably, to use the Saururus chinensis extract as a pharmaceutical composition, a pharmaceutically acceptable additive may be added, and a pharmaceutically acceptable additive may be added for use as a health functional food.

Experimental Example  1. Changes in pulse pressure and atrial ejection fraction according to the concentration of Saururus chinensis extract (1)

This study was conducted to investigate the effects of spermatozoa extract concentration and pulse pressure It was carried out to see the change.

(1) Experimental process

FIG. 1 is a view showing a design diagram at the time of manufacturing the atrial ventricular perfusion model.

1) Model of atrial pumping

1.82 kg of New Zealand white rape was used as an experimental animal. The rabbits were treated with ketamine-HCl (50 mg / kg, i.v.) and immediately anesthetized, bleeding was performed, and the heart was harvested.

② The extracted heart was transferred to physiological saline solution at 34 ℃ containing oxygen and the left atrium was separated.

③ A 4 mm outer diameter canula (canula) made of 3 polyethylene (PE) tubes embedded in the atrium was fixed to the atrium. At this time, it was fixed so as to be located up to a depth of 2.5 mm. One of the three PE tubes was used to inject the nutrient solution into the atrium, the other to measure the flow of the perfusion solution, and the other to measure the pressure inside the atrium.

The cannula was scribed and platinum wire was buried in the cannula to provide electrical stimulation.

④ The atrium with fixed cannula was immediately transferred to a 3-pass double perfusion device and stimulated with electric stimulation of 0.3 ~ 0.5 ms and 30 ~ 40V.

In the perfusion device, 3 ml of the same solution as the perfusion solution was injected, and oxygen was supplied to the silicon tube inside the perfusion device. The perfusate was also continuously infused with a beating infusion pump (1 ml / min).

The perfusion solution was composed of 118 NaCl, 4.7 KCl, 2.5 CaCl ₂ , 1.2 MgCl ₂ , 25 NaHCO ₃ , 10 glucose, 10 HEPES and 0.1% bovine serum albumin (BSA) , and the pH is 7.4.

(5) Pressure fluctuations in the atria were continuously measured using a Power Lab / 8sp (model ML 785, AD Instrument, Australia).

⑥ One atrial ejection fraction was measured by measuring changes in the water column in the cannula during atrial diastole and systolic period.

2) Measurement of changes in pulsation pressure and atrial ejection during treatment with Saururus chinensis extract

Four groups of atrial ventricular perfusion models were prepared and the two groups were treated with 10 ^-3 g / ml and 10 ^-4 g / ml of Saururus chinensis extract 6 minutes after the start of the measurement and the pulse pressure was measured.

The remaining two groups were also treated with 10 ^-3 g / ml and 10 ^-4 g / ml of Saururus chinensis extract at the beginning of the measurement and the amount of atrial ejection was measured once.

Measurements were carried out up to 42 minutes after treatment with Saururus chinensis extract and measured in 6 minute increments.

(2) Experimental results

FIG. 2 is a graph showing the results of measurement of the pulse pressure and the amount of one-time atrial ejection when the Saururus chinensis extract was treated at 10 ^-3 g / ml.

FIG. 3 is a graph showing the results of measurement of the pulse pressure and the amount of one-shot atrial discharge when the Saururus chinensis extract was treated at 10 ^-4 g / ml.

The extract was three hundred seconds 10 ^-3 g / ml treatment group with 10 ^-4 g / ml treatment group compared to the results, in the Houttuynia cordata extract 10 ^-3 g / ml treatment group pulse pressure and stroke volume is constant once the atrial aspect of this increase.

The Houttuynia cordata extract 10 ^-4 g / ml treatment group with the lapse of time as the pulse pressure, and once the atrial cardiac output decreases, and it was confirmed that the change in extent is similar to the control group.

Thus, it can be concluded that the treatment of Saururus chinensis extract at 10 ^-3 g / ml or more increases pulse pressure and one-time atrial ejection, that is, myocardial contraction.

Experimental Example  2. Changes in pulse pressure and one-time atrial ejection according to the concentration of Saururus chinensis extract (2)

The present experiment was conducted in the same manner as in Experimental Example 1 except that the pulse pressure and the amount of one-time atrial ejection It was implemented to learn more about changes.

(1) Experimental process

1) Model of atrial pumping

The same procedure as described in Experimental Example 1 was carried out.

2) Measurement of change in pulse pressure and atrial ejection fraction according to the concentration of Saururus chinensis extract

Atrial beats perfusion model, the three groups prepared in Houttuynia cordata extract 10 in the untreated group, ^{respectively, -3 g / ml, 10 -4} g / ml , and the treatment were measured and the amount of change in pulse pressure, and the remaining two groups also Houttuynia cordata extract ^10-3 g / ml, 10 ^-4 g / ml, and the change in atrial ejection fraction was measured once.

(2) Experimental results

FIG. 4 is a graph comparing the results of measuring the pulse pressure and the amount of one-time atrial ejection when the concentration of Saururus chinensis extract was changed to 10 ^-3 g / ml and 10 ^-4 g / ml.

As a result of the experiment, Saururus chinensis extract significantly increased the pulse pressure and the one atrial ventricular output in a concentration dependent manner. Houttuynia cordata extract 10 ^-3 g / ml treatment group with 10 ^-4 g / ml compared to the group treated with the present results, particularly Houttuynia cordata extract 10 ^-3 g / ml treatment group, pulse pressure, and once the atrial cardiac output was higher significantly in.

At 10 ^-4 g / ml of Saururus chinensis extract, pulse pressure and one atrial output were slightly higher than the control group. The amount of change in the pulse pressure of the Houttuynia cordata extract 10 ^-4 g / ml treatment group was 8 △%, 1 times atrial stroke volume variation was 25% △.

The change in the pulse pressure of the Saururus chinensis extract treated with 10 ^-3 g / ml was 220 △%, and the change of the atrial ejection amount was also 220 △%.

As a result, it can be concluded that Saururus chinensis extract increases pulse pressure and one atrial ejection.

Experimental Example  3. Myocardial contraction inducing activity of Saururus chinensis extract

Typical myocardial contraction mechanism of L- type Ca ^{+ 2} channel passage (L-type Ca channel pathway) takes place by way of a, L- type Ca ^{2 +} drug which is widely used as a channel inhibitor nifedipine (nifedifine) and diltiazem (diltiazem )to be.

This experiment aforementioned two types of L- type Ca ^{2 +} and then to the pre-treatment channel inhibitors disable L- type Ca ^{+ 2} channel path, together with the Houttuynia cordata extract two types of L- type Ca ^{2 +} channel inhibitor treatment The changes of pulse pressure and 1 atrial output were measured and the effect of Saururus chinensis extract on myocardial contractility was investigated.

(1) Experimental process

1) Model of atrial pumping

The same procedure as described in Experimental Example 1 was carried out.

2) Comparing changes in pulse pressure and one-time atrial ejection during pretreatment of nifedipine or diltiazem and in combination with nifedipine or diltiazem treatment

Four groups of atrial ventricular perfusion models were prepared. Two groups were treated with 1 μM of nifedipine 6 minutes after the start of the measurement, and then treated with 10 ^-3 g / ml of Saururus chinensis extract and 1 μM of nifedipine 24 minutes after the start of the measurement.

The remaining two groups were treated with 1 uM of diltiazem 6 minutes after the start of the measurement, and then treated with 10 ^-3 g / ml of Saururus chinensis extract and 1 uM of diltiazem after 24 hours from the start of the measurement. Pulsatile pressure and one ventricular ejection fraction were measured in these four groups.

Measurements were carried out up to 60 minutes after treatment with Saururus chinensis extract and measured in 6 minute increments.

(2) Experimental results

FIG. 5 is a graph showing the results of measurement of changes in pulse pressure and one-time atrial ejection when nifedipine alone was treated and when 10 ^-3 g / ml of nifedipine and Saururus chinense extract were treated.

FIG. 6 is a graph showing the results of measuring changes in pulse pressure and one-time atrial ejection when diltiazem was treated alone and when diltiazem and Saururus chinense extract were treated with 10 ^-3 g / ml.

Experimental results show that the pretreatment of nifedipine reduces pulse pressure and one time of atrial expulsion for 36 minutes and pretreatment of diltiazem for 24 minutes. In other words, myocardial contraction is reduced.

In addition, when the nifedipine or diltiazem was pretreated and the Saururus chinensis extract and the nifedipine or Saururus chinensis extract were combined with diltiazem, the pulse pressure and the one atrial discharge were almost the same as those in the case of the Saururus chinensis extract alone in Experimental Example 1 Of the total. In other words, myocardial contraction is increased again.

In summary, pretreatment of the L-type Ca ^{2 +} channel channel inhibitor, nifedipine or diltiazem, with the atrial stroke perfusion model resulted in a decrease in myocardial contractility, but subsequent treatment of nifedipine and Saururus chinensis extract or Diltiazem and Saururus chinensis extract , Myocardial contraction increased again.

Therefore, it can be concluded that Saururus chinensis extract has the effect of increasing myocardial contractility even in combination with nifedipine or diltiazem.

Also, Houttuynia cordata extract can derive a conclusion that cause myocardial contraction via other mechanisms without going through the normal myocardial contraction mechanism of L- type Ca ^{+ 2} channel passage.

Claims (5)

A composition for preventing, ameliorating, or treating heart failure, comprising Saururus chinensis extract as an active ingredient.
The method according to claim 1,
Wherein the composition has the effect of increasing pulse pressure and stroke volume. ≪ RTI ID = 0.0 > 11. < / RTI >
The method of claim 2,
The composition according to any one of claims 1 to 5, wherein the composition is used for preventing, ameliorating or treating heart failure, wherein the heart rate is increased by 8 to 220% and the atrial output is increased by 25 to 220%.
The method according to claim 1,
Wherein the concentration of said composition is 10 < ^-3 > g / ml based on a rabbit atrial pacing model.
A health functional food for preventing, ameliorating or treating heart failure, comprising a composition according to any one of claims 1 to 4 and containing a pharmaceutically addable additive.

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