KR102186532B1 - Composition for preventing or treating a hypertensive disease comprising extract of Indigofera pseudotinctoria Matsum or fraction thereof as active ingredient - Google Patents

Abstract

The present invention includes a pharmaceutical composition for the prevention or treatment of hypertensive diseases, comprising the extract or a fraction thereof as an active ingredient; Indigofera pseudotinctoria Matsum; And it relates to a food composition for preventing or improving hypertensive diseases.
Since the cystoid extract or a fraction thereof of the present invention relaxes constricted blood vessels to confirm the preventive or therapeutic effect of hypertensive diseases, the composition comprising the same includes hypertension, stroke, heart failure, myocardial infarction, arrhythmia, heart failure, coronary atherosclerosis, It can be effectively used for the prevention or treatment of hypertensive diseases such as hypertensive retinopathy, aortic dissection, and hypertensive neurosis.

Description

Composition for preventing or treating a hypertensive disease comprising extract of Indigofera pseudotinctoria Matsum or fraction thereof as active ingredient, comprising cystoid extract or a fraction thereof as an active ingredient}

The present invention is a pharmaceutical composition for the prevention or treatment of hypertensive diseases, comprising an extract or a fraction thereof as an active ingredient of cysticacho ( Indigofera pseudotinctoria Matsum); It relates to a food composition for preventing or improving hypertensive diseases.

Due to the aging population, hypertension is a major disease with increasing incidence in most countries. Hypertension by itself does not present any serious symptoms, but is one of the major risk factors for cardiovascular disease (CVD). About 45% of deaths from heart disease and about 51% of deaths from stroke are due to high blood pressure.

Clinically, the pathogenesis of hypertension seems to be mostly due to impaired blood vessel constriction and blood vessel relaxation ability, and this physiological action becomes an important factor in inducing pathological hypertension when it fails to respond to changes in blood pressure. In view of the characteristic of maintaining increased resistance of peripheral blood vessels in most of the early and advanced hypertension, the regulation of vascular tone is an important factor in the control of blood pressure. Representative factors that relax blood vessels include endothelial cell-derived factors, Ca ²⁺ and K ⁺ pathways in vascular smooth muscle, and autonomic nervous system. Vascular relaxation factors such as nitric oxide (NO), prostacyclin (PGI ₂ ), bradykinin, and endothelial-derived hyperpolarization factor (EDHF), which are produced in vascular endothelial cells, relax the blood vessels, and endoceline ( endothelin) and angiotensine Ⅱ. Vascular smooth muscle as well as vascular endothelial cells play an important role in the contraction and relaxation of blood vessels. There are Ca ²⁺ pathway and K ⁺ pathway as mechanisms that control the contraction and relaxation of blood vessels in vascular smooth muscle, and are determined by various actions such as changes in cell membrane voltage, contraction, and relaxation regulators formed by the flow of ions.

Currently, various drugs such as calcium channel blocker (CCB), angiotensin converting enzyme inhibitor, angiotensin II receptor blocker (ARB), beta blockers, and diuretics are used to treat hypertension. have. However, the above synthetic drugs may cause side effects or complications, so caution is required. Therefore, there is a need for research to find a substance for preventing or treating cardiovascular diseases from herbal medicines or medicinal plants that are safe with little side effects.

Indigofera pseudotinctoria Matsum is a deciduous broad-leaved semi-shrub that grows wild in the coastal areas of Gyeongsang-do, Jeolla-do, and Jeju-do of Korea. It reaches 2 m in height and grows by splitting branches with coat hair. The cyst is distributed not only in Korea, but also in Japan and China.

In addition, cystocarp was first introduced as a medicinal herb in Guhwangboncho (救荒本草), and the above-ground part and root of cystocarp were used for the treatment of influenza, acute pneumonia, pulmonary tuberculosis, malaria, bruises, social wounds, and mastitis (Zhong Hua Ben Cao Commission). , 1999). According to a recent study, cystoids showed burn treatment (Liu Wei. Zheng Yan, 2011), hemostatic effect (Hu Ze-hua, 2009), and anti-inflammatory effect (Zhou Jing, 2012). In other words, there has been no report on the vasodilating effect of cystocarps extract.

Under this background, the present inventor completed the present invention by confirming the effect of preventing or treating hypertensive diseases through which extracts of various parts of cystoids exhibit a blood vessel (thoracic aorta) relaxation effect.

Zhong Hua Ben Cao Commission (1999) Zhong Hua Ben Cao (Materia Medica of China). Liu Wei and Zheng Yan (2011), Research on the preparation of Indigofera pseudotinctoria Matsum ointment and its therapeutic effects of treating laboratorial scald, Chinese J Hosp Pharm. Hu Ze-hua (2009), The Haemostatic Effect of Indigofera Pseudotinctoria Mats on Mouse, J Hubei Univ Natl Ed. Zhou Jing (2012), The Studies on the Anti-inflammatory Chemical Constitutes from Indigofera Pseudotinctoria Mats.

One object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of hypertensive diseases, comprising an extract or a fraction thereof as an active ingredient of Indigofera pseudotinctoria Matsum.

Another object of the present invention is to provide a food composition for preventing or improving hypertensive diseases, comprising an extract of Indigofera pseudotinctoria Matsum or a fraction thereof as an active ingredient.

Each description and embodiment disclosed in the present invention can be applied to each other description and embodiment. That is, all combinations of various elements disclosed in the present invention belong to the scope of the present invention. In addition, it cannot be seen that the scope of the present invention is limited by the specific description described below.

As an aspect for achieving the above object, the present invention provides a pharmaceutical composition for the prevention or treatment of hypertensive diseases, comprising a cystweed extract or a fraction thereof as an active ingredient.

In the present invention, the term "cystoid" is the scientific name Indigofera pseudotinctoria Matsum, and various parts of the cystoid can be extracted and used in the present invention. Specifically, seeds, leaves, or roots of the cysts may be used, and more specifically, roots may be used, but as long as it has a preventive or therapeutic effect on hypertensive diseases, it is not particularly limited thereto. Does not.

The cysts can be purchased commercially sold, or those harvested or cultivated in nature can be used without distinction.

The term "extract" of the present invention refers to an extract obtained by extracting cystoids, a diluent or concentrate of the extract, a dried product obtained by drying the extract, a crude purified product or purified product of the extract, or a mixture thereof , The extract itself and all formulations that can be formed using the extract are included.

The cystocarp extract can be extracted from various organs of natural, hybrid, and mutant plants, and can be produced by extracting from cystoid tissue cultures as well as seeds, leaves, roots, and stems, and in particular using cystoid roots. However, it is not limited thereto.

The method of extracting the cystoid is not particularly limited, and may be extracted according to a method commonly used in the art. Non-limiting examples of the extraction method include a hot water extraction method, an ultrasonic extraction method, a filtration method, a reflux extraction method, and the like, which may be performed alone or in combination of two or more methods.

In the present invention, the type of the extraction solvent used to extract the cysts is not particularly limited, and any solvent known in the art may be used. Non-limiting examples of the extraction solvent include water, C1 to C4 alcohol, and a mixed solvent thereof, and these may be used alone or in combination of one or more. More specifically, the extraction solvent of the cystocarps extract may be ethanol, for example, 70% ethanol, but is not limited thereto.

In addition, the extract may be prepared and used in a dry powder form after extraction, but is not limited thereto.

As used herein, the term "fraction" means a result obtained by performing fractionation in order to separate a specific component or a specific group of components from a mixture containing several different constituents.

The fractionation method for obtaining the fraction in the present invention is not particularly limited, and may be performed according to a method commonly used in the art. Non-limiting examples of the fractionation method include a fractionation method performed by treating various solvents, an ultrafiltration fractionation method performed by passing through an ultrafiltration membrane having a certain molecular weight cut-off value, and various chromatography (size, charge, hydrophobicity or A chromatographic fractionation method for performing separation according to affinity), and combinations thereof. Specifically, there may be mentioned a method of obtaining a fraction from the extract by treating the extract obtained by extracting the cystocarps of the present invention with a predetermined solvent.

In the present invention, the type of fractionation solvent used to obtain the fraction is not particularly limited, and any solvent known in the art may be used. Non-limiting examples of the fractionation solvent include polar solvents such as water and alcohols having 1 to 4 carbon atoms; Non-polar solvents such as hexane, ethyl acetate, chloroform, and dichloromethane; Or a mixed solvent of these, etc. are mentioned. These may be used alone or in combination of one or more, but are not limited thereto, and specifically, hexane, ethyl acetate, butanol, or water may be used alone or as a mixture of one or more, but is limited thereto. It does not become.

In addition, the fraction may be prepared and used in a dry powder form after fractionation, but is not limited thereto.

The present invention is based on the technical idea that cystoid extract or a fraction thereof has a prophylactic or therapeutic effect of hypertensive disease, specifically, a vascular relaxation effect, which was first identified by the present inventors.

As used herein, the term "hypertensive disease" refers to a disease related to hypertension, which occurs when a systolic blood pressure is 140 mmHg or more or a diastolic blood pressure is 90 mmHg or more in an adult 18 years of age or older. If the state of high blood pressure persists for a long time, various complications occur in each part of the body, and sometimes fatal symptoms such as heart attack or stroke appear. Types of such hypertensive diseases include hypertension, hemorrhagic stroke, ischemic stroke, heart failure, myocardial infarction, arrhythmia, heart failure, coronary atherosclerosis, hypertensive retinopathy, aortic dissection, hypertensive neurosis, but by the above examples, the present invention The type of hypertensive disease is not limited. Specifically, the hypertensive disease may be a disease exhibiting a therapeutic effect by relaxation of blood vessels, but is not limited thereto.

The term "prevention" of the present invention refers to any action of inhibiting or delaying the progression of hypertensive disease by administration of the pharmaceutical composition of the present invention comprising cystoid extract or a fraction thereof.

The term "treatment" of the present invention refers to any action in which hypertensive disease is improved or beneficially altered by administration of the pharmaceutical composition.

In the present invention, the therapeutic effect of hypertensive diseases may be achieved by relaxing constricted blood vessels. Specifically, in one embodiment of the present invention, when the cystoid extract of the present invention is treated with phenylephrine HCl (PE) on a section of a blood vessel (thoracic aorta) induced contraction, the blood vessels are significantly relaxed to treat hypertensive diseases. It was confirmed that the effect was shown.

The "pharmaceutical composition" of the present invention may further include a pharmaceutically acceptable carrier, excipient or diluent commonly used in the preparation of pharmaceutical compositions, and the carrier is a non-naturally occurring carrier. It may include.

The pharmaceutical compositions may be formulated and used in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc., external preparations, suppositories, and sterile injectable solutions, respectively, according to conventional methods. .

The "pharmaceutically acceptable" means exhibiting properties that are not toxic to cells or humans exposed to the composition.

Specifically, the type of the carrier is not particularly limited, and any carrier commonly used in the art and pharmaceutically acceptable may be used. Non-limiting examples of the carrier include saline, sterile water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, ethanol, and the like. These may be used alone or in combination of two or more. In addition, if necessary, other conventional additives such as antioxidants, buffers and/or bacteriostatic agents can be added and used, and diluents, dispersants, surfactants, binders, lubricants, etc. can be additionally added to provide main solutions such as aqueous solutions, suspensions, and emulsions. It can be formulated and used as a dosage form, pill, capsule, granule, or tablet.

A method of administering the pharmaceutical composition for preventing or treating hypertensive diseases according to the present invention is not particularly limited, and may be according to a method commonly used in the art. As a non-limiting example of the administration mode, the composition may be administered orally or parenterally. In addition, the composition for preventing or treating hypertensive diseases of the present invention may be prepared in various formulations according to the intended administration method.

In another aspect of the present invention, it provides a food composition for preventing or improving hypertensive diseases, comprising a cystweed extract or a fraction thereof as an active ingredient.

At this time, the description of the cyst, extract, fraction, hypertensive disease, and prevention are as described above. In addition, the vasodilator effect of the cystoid extract of the present invention or a fraction thereof, and the therapeutic effect of hypertensive diseases through the same are as described above.

As used herein, the term "food" refers to meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages , Vitamin complexes, health functional foods, and health foods, and all foods in the usual sense are included.

Since the food composition of the present invention can be ingested on a daily basis, it can be expected to improve high blood pressure diseases, and thus can be very usefully used for health promotion purposes.

The health function (functional food) is the same term as food for special health use (FoSHU).In addition to nutritional supply, the term "functional food" refers to medicine that is processed so that the bioregulatory function is effectively displayed. Means food. Here, the term'function (sex)' means to control nutrients for the structure and function of the human body or to obtain useful effects for health purposes such as physiological actions. The food of the present invention can be prepared by a method commonly used in the art, and during the production, raw materials and ingredients commonly added in the art may be added to prepare the food product. In addition, the formulation of the food may be prepared without limitation as long as it is a formulation recognized as a food. The food composition of the present invention can be prepared in various forms, and unlike general drugs, it has the advantage of not having side effects that may occur when taking drugs for a long time using natural substances as raw materials, and is excellent in portability. The food of the present invention can be consumed as an adjuvant for enhancing the effect of improving hypertensive diseases.

The health food refers to a food having an active health maintenance or promotion effect compared to a general food, and a health supplement food refers to a food for health supplement purposes. In some cases, the terms health functional food, health food, and health supplement food are used interchangeably.

Specifically, the health functional food is a food prepared by adding the extract of the present invention to food materials such as beverages, teas, spices, gums, confectionery, or encapsulating, powdering, and suspending. It means bringing about an effect, but unlike general drugs, it has the advantage of not having side effects that may occur when taking the drug for a long time because it is made from food.

The food composition may further include a physiologically acceptable carrier, the kind of carrier is not particularly limited, and any carrier commonly used in the art may be used.

In addition, the food composition may include additional ingredients that are commonly used in food compositions to improve smell, taste, vision, and the like. For example, vitamins A, C, D, E, B1, B2, B6, B12, niacin, biotin, folate, panthotenic acid, and the like may be included. In addition, minerals such as zinc (Zn), iron (Fe), calcium (Ca), chromium (Cr), magnesium (Mg), manganese (Mn), copper (Cu), and chromium (Cr); And amino acids such as lysine, tryptophan, cysteine, and valine.

In addition, the food composition includes preservatives (potassium sorbate, sodium benzoate, salicylic acid, sodium dehydroacetate, etc.), disinfectants (bleaching and highly bleaching, sodium hypochlorite, etc.), antioxidants (butylhydroxyanisol (BHA), butylhydride, etc.) Oxytoluene (BHT), etc.), coloring agent (tar color, etc.), coloring agent (sodium nitrite, sodium nitrite, etc.), bleach (sodium sulfite), seasoning (MSG sodium glutamate, etc.), sweetener (dulsin, cyclamate, saccharin, etc.) Sodium, etc.), flavoring (vanillin, lactones, etc.), expanding agents (alum, D-potassium hydrogen stannate, etc.), reinforcing agents, emulsifying agents, thickening agents (flavoring agents), coating agents, gum base agents, foam inhibitors, solvents, improving agents, etc. (food additives). The additive may be selected according to the type of food and used in an appropriate amount.

Since the cystoid extract or a fraction thereof of the present invention relaxes constricted blood vessels to confirm the preventive or therapeutic effect of hypertensive diseases, the composition comprising the same includes hypertension, stroke, heart failure, myocardial infarction, arrhythmia, heart failure, coronary atherosclerosis, It can be effectively used for the prevention or treatment of hypertensive diseases such as hypertensive retinopathy, aortic dissection, and hypertensive neurosis.

FIG. 1 shows the results of confirming the vasodilating effect of cystocarps extract on constricted thoracic aortic sections by treatment with PE (phenylephrine hydrochloride), and FIG. 1A shows extracts of various parts (seeds, leaves, roots) of cystocarps at various concentration It shows the vascular relaxation curve when administered to the constricted blood vessel, and Fig. 1B shows the vascular relaxation effect, in particular, when the cystoid root extract is treated.

Hereinafter, the present invention will be described in more detail through examples and experimental examples. However, these Examples and Experimental Examples are for illustrative purposes only, and the scope of the present invention is not limited to these Examples and Experimental Examples.

Example 1. Preparation of cystocarp extract

1-1: cysts

Indigofera pseudotinctoria Matsum, used in this experiment, was collected in Bugang-myeon, Sejong-si, Korea in November 2011, and is kept in the Department of Herbal Medicine, College of Oriental Medicine, Kyunghee University after plant identification.

1-2: Cystic extract preparation

100 g of dried seeds, leaves, and roots were extracted three times at 70±5° C. for 3 hours with 1 L of 70% ethanol. Each extract was filtered through a filter paper, concentrated with a vacuum concentrator, and lyophilized to obtain a solid extract.

In subsequent vasodilating experiments, each extract was dissolved in a Krebs-Henseleit (KH) buffer at a concentration of 0.1 g/ml and used.

Experimental Example 1. Vascular relaxation effect of cystocarp extract

1-1: experimental animals

Experimental animals are male rats weighing 200 to 300 g (Raon Bio, Yongin, Korea), supplied with solid feed (Biopia, Korea) and water for a week in a laboratory environment (22±2 ℃; lightning, 07:00-). 19:00) and used in the experiment. All animals used in the experiment complied with the animal welfare guideline of the Animal Ethics Committee of Kyunghee University.

1-2: reagent

In the present invention, among various drugs that have an effect on vasoconstriction, phenylephrine hydrochloride (PE) was used.

Specifically, phenylephrine hydrochloride (PE) releases calcium stored in the muscle vesicles (IP ₃ R pathway), or opens a receptor-operated calcium channel (ROCC), and calcium To constrict blood vessels. Accordingly, phenylephrine hydrochloride (PE) was used as an agonist of vasoconstriction because it is suitable for verification of the vasoconstriction effect of cystoid extract on calcium channels and vascular endothelial cells, which are representative mechanisms for contracting and relaxing vascular smooth muscle. .

Phenylephrine hydrochloride (PE) is manufactured by Wako in Japan, calcium chloride (CaCl ₂ ) and glucose are manufactured by Sigma in the United States, sodium chloride (NaCl), sodium hydrogen carbonate (NaHCO ₃ ), urethane (urethane) and ethanol are manufactured by Daejeong Chemical Korea. , Potassium monophosphate (KH ₂ PO ₄ ), potassium chloride (KCl), and anhydrous magnesium sulfate (MgSO ₄ ) were manufactured by Deoksan Pharmaceutical Korea.

1-3: device

A polygraph (Grass instrument Co., USA) equipped with a force-displacement transducer and PowerLab (ADI instrument CO., Australia) were used.

1-4: Preparation and preparation of vascular section

Rats were anesthetized by intraperitoneal administration of urethane at a concentration of 1.5 g/kg, and then the thoracic aorta was excised by incising the chest immediately. The extracted blood vessels were supplied with a mixed gas (95% O ₂ and 5% CO ₂ ) and maintained at 37° C. KH buffer (composition, mM: NaCl, 118.0; KCl, 4.7; MgSO ₄ , 1.2; KH ₂ PO ₄₎ , 1.2; CaCl ₂ , 2.5; NaHCO ₃ , 25.0; and glucose, 11.1; pH 7.4) was immediately added to remove tissue and fat around blood vessels, and then cut into a ring shape of about 3 mm in length to prepare a vascular section.

Each of the upper and lower portions of the vessel section was hung with a tungsten ring. The lower part is connected to a ring mounted on the bottom of an organ bath, and the upper part is connected to an isometric force transducer connected to a physiograph, and the change of isotonic contraction is monitored by PowerLab (ADI instrument). CO., Australia) program. The tissue bath was filled with 10 ml KH buffer, and the mixed gas (95% O ₂ and 5% CO ₂ ) was always supplied during the experiment and maintained at 37°C.

The vascular section was stabilized in a tissue bath for 20 minutes, and then 1.2 g of passive tension was applied, and after being stabilized for 20 minutes, the next experiment was conducted. During stabilization, the KH buffer in the tissue bath was changed to a fresh solution every 10 minutes.

1-5: Measurement of blood vessel tension change

In order to confirm the vasodilating activity of the three cystoid extracts prepared in Example 1, the thoracic aortic section of the rat was contracted with PE (1 μM), and when the maximum contraction was reached, the three cystoid extracts were mixed at various concentrations (10, 30, 100, 300, 1000 ㎍ / ㎖) was measured after administration of the blood vessel tension change. The control group was a group that was not treated with cystocarp extract.

1-6: statistical processing

All measurement results were expressed as mean±standard error (mean±SEM), and for the test of the difference between the control group and the experimental group, a Student's T-test was performed using SPSS 23.0, and the significance was determined as p <0.05.

1-7: result

The effects of the three types of cystocarps extracts on blood vessels induced contraction by PE are shown in Fig. 1 and Table 1.

As a result of administration of cystocarps seed extract, leaf extract, or root extract by concentration (10 ~ 1,000 µg/ml), relaxation effect increased as the dose concentration increased in all three extracts, 22.9±1.8%, respectively, at 1,000 µg/ml concentration, It showed excellent relaxation effect of 44.2±4.9% and 95.2±0.4%. In particular, when administered at 1,000 ㎍ / ㎖ of cystic root extract showed a relaxation effect of 95.2±0.4%, it was confirmed that the remarkably excellent relaxation effect was shown (Fig. 1 and Table 1).

[Table 1]

From the above results, it was confirmed that various cystoid extracts had a concentration-dependent vascular relaxation effect on all thoracic aortic sections of rats contracted with PE (FIG. 1 and Table 1). It can be inferred that it exhibits an effect through the IP ₃ R pathway or through a mechanism of blocking receptor-acting calcium channels (ROCC) or vascular relaxation factors derived from vascular endothelial cells. It was confirmed that it can be used in the prevention or treatment of hypertensive diseases through the effect of vascular relaxation.

From the above description, those skilled in the art to which the present invention pertains will be able to understand that the present invention can be implemented in other specific forms without changing the technical spirit or essential features thereof. In this regard, it should be understood that the embodiments described above are illustrative in all respects and not limiting. The scope of the present invention should be construed that all changes or modifications derived from the meaning and scope of the claims to be described later rather than the above detailed description, and equivalent concepts thereof, are included in the scope of the present invention.

Claims (9)

As a pharmaceutical composition for preventing or treating hypertensive diseases, comprising an extract of Indigofera pseudotinctoria Matsum or a fraction thereof as an active ingredient,
The pharmaceutical composition that the extract is extracted with water, an alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof.
The pharmaceutical composition of claim 1, wherein the extract is extracted from cystoid seeds, cystoid leaves or cystoid roots.
The pharmaceutical composition according to claim 1 or 2, wherein the composition has a vasodilating effect.
delete The method of claim 1 or 2, wherein the hypertensive disease is selected from the group consisting of hypertension, hemorrhagic stroke, ischemic stroke, heart failure, myocardial infarction, arrhythmia, coronary atherosclerosis, hypertensive retinopathy, aortic dissection, and hypertensive neurosis. Which, pharmaceutical composition.
As a food composition for preventing or improving hypertensive diseases, comprising an extract of Indigofera pseudotinctoria Matsum or a fraction thereof as an active ingredient,
The food composition that the extract is extracted with water, alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof.
The food composition according to claim 6, wherein the composition is extracted from cystoid seeds, cystoid leaves or cystoid roots.
The food composition according to claim 6 or 7, wherein the composition has a blood vessel relaxation effect.
The method of claim 6 or 7, wherein the hypertensive disease is selected from the group consisting of hypertension, hemorrhagic stroke, ischemic stroke, heart failure, myocardial infarction, arrhythmia, coronary atherosclerosis, hypertensive retinopathy, aortic dissection, and hypertensive neurosis. That, food composition.

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