KR20180097974A - Composition for vasorelaxant effect comprising extract or hydrolyzed extract of dendropanax morbifera - Google Patents

Abstract

The present invention relates to a composition for preventing, ameliorating or treating vascular diseases comprising an extract of Dendropanax morbifera or a hydrolysate thereof. More particularly, the present invention relates to a pharmaceutical composition and a health supplement food for preventing, ameliorating or treating vascular diseases which can relax blood vessels by comprising the extract of Dendropanax morbifera or the hydrolysate of Dendropanax morbifera manufactured by treating the extract of Dendropanax morbifera with enzymes.

Description

FIELD OF THE INVENTION [0001] The present invention relates to a composition for vascular restenosis comprising a woodchuck extract or a hydrolyzate thereof. BACKGROUND OF THE INVENTION < RTI ID = 0.0 >

The present invention relates to a composition for preventing or treating a vascular disease, comprising an extract of Hwangchujang or a hydrolyzate thereof, and more particularly, to a composition for preventing or treating vascular diseases of a Hwangcholguk extract or a hydrolyzate thereof, ≪ / RTI > pharmaceuticals and health supplements.

The smoothness of the vascular smooth muscle is determined by several factors, and it is generally known that a pathway of NO-cGMP (nitric oxide-cyclic guanosine monophosphate) acts as an important pathway. Nitric oxide (NO), which is a neurotransmitter, is produced from L-arginine by endothelial nitric oxide synthase (NOS) in endothelial cells. NO produced activates soluble guanulate cyclase (sGC) Relax the vascular smooth muscle through the system.

Vasoconstriction is the narrowing of blood vessels, including the aorta, small arteries, and veins, as the vessel wall contracts. Vascular disorders caused by contraction of blood vessels include arteriosclerosis, blood circulation disorder, hypertension, headache, stroke, cerebral infarction, cerebral hemorrhage, myocardial infarction and heart failure. For the treatment of these diseases, vasodilators are administered. However, the conventional chemical vasodilator has been known to cause side effects such as endothelial damage, hemolysis, acute toxicity or fish toxicity, acute nephritis or heart attack in vivo, and the production process is complicated and mass production is not easy.

The use of natural-product-derived compositions has been increasing worldwide. Dendropanax morbifera Lev . ) Is an evergreen broad-leaved arboreous tree native to the southern coast of Korea and Jeju-do. It is a species that does not fall into winter when it blooms in the winter. When it bruises the bark, yellowish resinous liquor is called 黄 漆. Huangchil has been used as a rare paint for the emperor's armor, helmet, and other metal ornaments since the Three Kingdoms period. It has been used in the Goryeo period, which was written in the Goryeo period, the Guilin variety in China, And it is said that it was a special product of Baekje which was before it, and it remains in the passage of the book department of the Tang history book. It is said that it is effective for burning removal, eye quality, burn treatment, leprosy, harmlessness, and it is used recently for tea and food.

KR 101668728 B1

An object of the present invention is to provide a composition for preventing, ameliorating or treating a vascular disease, comprising an extract of Hwangcholgwa or a hydrolyzate thereof as an active ingredient.

According to one aspect of the present invention, there is provided a dendropanax Morbifera extract or a hydrolyzate thereof as an active ingredient is provided.

In addition, the hydrolyzate may include an enzyme treatment step of treating proteolytic enzyme in the extract of Hwangchujang; And an inactivation step of inactivating the treated enzyme.

In addition, the enzyme treatment step may include a first step of treating Bacillus subtilis- derived protease, trypsin and chymotrypsin; And a second step of treating bromelain and papain.

In addition, pepsin may be further treated in the first step.

In addition, the ficin may be further processed in the second step.

In addition, the vascular diseases may be selected from the group consisting of hypertension, arteriosclerosis, peripheral blood circulation disorder, cerebral infarction, angina pectoris, myocardial infarction and ischemic brain disease.

In addition, the extract of Huacarmin or its hydrolyzate may have vasodilatory action.

According to another aspect of the invention, the Dendropanax Morbifera extract or a hydrolyzate thereof as an active ingredient for the prevention or treatment of vascular diseases.

According to another aspect of the invention, the Dendropanax Morbifera extract or a hydrolyzate thereof as an active ingredient is provided.

According to one aspect of the present invention, the composition comprising the extract of Hwigulak extract or hydrolyzate thereof may be used for the purpose of preventing, ameliorating or treating vascular diseases through relaxation of blood vessels.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a process diagram for producing the hydrolyzed extract of P. falciparum of the present invention,
FIG. 2 shows that the vascular tissue of the mouse thoracic aorta contracted with phenylephrine was relaxed by acetylcholine,
FIG. 3 is a graph showing the effect of hydrothermal extract of Huangchu tree on relaxation of vascular tissues of mouse thoracic aorta,
Fig. 4 shows the effect of hydrolyzed extract of Hwangryeok tree on relaxation of vascular tissues of mouse thoracic aorta.

The invention hwangchil tree (Dendropanax Morbifera extract or a hydrolyzate thereof as an active ingredient for the prevention or treatment of vascular diseases.

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

The composition of the present invention contains extracts of Hokutogi or its hydrolyzate as active ingredients.

The part of the perennial tree which can isolate the perennial extract may be at least one selected from the group consisting of leaves, branches, roots and fruits of the perennial tree, but is not limited thereto. It is preferred that leaves or branches of Hwangryeok tree are selected. It is more preferable that the leaves or branches of Hwigae-gil are selected. The young branch means branches of one year old or younger. This can be cut, dried and pulverized by a conventional method. The drying method is not particularly limited, and a usual method can be used. For example, natural drying, hot air drying or freeze-drying can be used.

The method for separating the extract is not particularly limited, but a method commonly used in the art can be used to produce the extract. For example, a method using an extraction device such as hot water extraction, immersion extraction, reflux cooling extraction, supercritical extraction, subcritical extraction, high temperature extraction, high pressure extraction and ultrasonic extraction, or a method using an adsorption resin containing XAD and HP-20 Method, but the present invention is not limited thereto. Preferably, it can be obtained by treatment with an extraction solvent, followed by concentration under reduced pressure.

As the extraction solvent, a polar solvent may be used. The polar solvent may include, but is not limited to, at least one selected from the group consisting of water, alcohol, acetic acid, dimethyl-formamide (DMFO), and dimethyl sulfoxide (DMSO). Examples of the alcohol include at least one selected from the group consisting of methanol, ethanol, propanol, butanol, n-propanol, iso-propanol, n-butanol, 1-pentanol, 2-butoxyethanol and ethylene glycol But is not limited thereto. Preferably, water, alcohol or a mixed solution thereof is used as the polar solvent. More preferably, water is extracted with hot water using an extraction solvent.

When extracting the extractant by treating the extracting solvent, the extracting solvent may be added at a ratio of 1 to 100 times the dry weight of the whole wood. Preferably, it is added in an amount of 5 to 20 times the dry weight of the whole wood. The temperature at which the extractant is separated by treating the extraction solvent may be 10 to 120 ° C. Preferably 30 to 100 < 0 > C. The extract may be extracted for 1 to 72 hours within the above-mentioned temperature range to isolate the extract. Preferably for 2 to 12 hours, more preferably for 3 to 7 hours.

The separated extract may be provided in the form of a liquid or solid powder having a controlled concentration by removing the solvent through filtration, concentration or drying. Preferably, in order to increase the concentration of the useful component and improve the shelf life, it is preferable to concentrate and freeze-dry to provide it in powder form. The method of filtration, concentration or drying is not particularly limited and can be carried out by a conventional method.

The Hwacheon-jinja hydrolyzate can be prepared by using the Hwacheon-myeon extract. Wherein the hydrolyzate of Hwangchu tree is an enzyme treatment step of treating proteolytic enzyme in Hwangchu tree extract; And an inactivation step of inactivating the treated enzyme. The enzyme treatment step can be performed in several steps. It is described that the embodiment of the present invention is divided into two stages. This is shown in Fig. In order to shorten the production time and process to improve the productivity, the enzyme treated in the same step is preferably treated with the mixed mixture.

In step 1 of the enzymatic treatment step, the protein hydrolyzing enzyme may be treated in the extract of Hokutogi tree to increase the protein elution amount. The protein hydrolase may include a protease derived from Bacillus subtilis . The protease derived from Bacillus subtilis may be treated in an amount of 0.1 to 1% by weight based on the weight of the extract. Preferably 0.2 to 0.5% by weight. The treatment of the protease derived from Bacillus subtilis may be carried out at a temperature of 30 to 45 캜 for 3 to 5 hours. If necessary, the protein hydrolyzing enzyme may further comprise a mixture of trypsin and chymotrypsin to decompose the protein into a polypeptide and a small number of amino acids. The mixture of trypsin and chymotrypsin may be treated with 0.1 to 1% by weight, preferably 0.2 to 0.5% by weight, based on the weight of the extract. If necessary, the protein hydrolyzing enzyme may further comprise pepsin. The pepsin may be treated with 0.1 to 1% by weight, preferably 0.2 to 0.5% by weight, based on the weight of the extract.

Next, it is possible to carry out the two steps of the enzyme treatment step in which the primary digestible tree hydrolyzate obtained in step 1 is used to digest the peptide and convert it into an amino acid. In step 2 of the enzymatic treatment step, the amino acid digesting enzyme may be treated with the primary hydrogenated wood hydrolyzate. The aminopeptide decomposing enzyme may include an enzyme derived from fruit. The fruit-derived enzyme may include bromelain, a pineapple-derived protease, or papain, a cysteine-based proteolytic enzyme derived from a papaya fruit-derived emulsion. Preferably, a mixture of bromelain and papain is included. The fruit-derived enzyme may be treated with 0.1 to 2% by weight based on the weight of the extract. Preferably 0.2 to 1% by weight. The treatment of the fruit-derived enzyme can be carried out at a temperature of 45 to 55 DEG C for 12 to 20 hours. Optionally, in order to optimize arginine amplification, the fruit-derived enzyme may further comprise ficin, a digestive enzyme-derived degradative enzyme. The encrustation may be treated with 0.1 to 1% by weight, preferably 0.2 to 0.5% by weight, based on the weight of the extract.

Next, an inactivation step may be performed to inactivate the treated enzyme. The hydrolyzate prepared in the enzyme treatment step may be heated at 100 to 120 ° C. for 30 to 1 hour to inactivate the hydrolyzate. Through this, it is possible to produce the hydrolyzate of the extract of Wuchu chrysanthemum which is amplified with arginine. The hydrolyzate of the Hokutogi tree extract may be provided in the form of a liquid or solid powder having a controlled concentration by removing the solvent through filtration, concentration or drying.

The composition comprising the extract of Eustachian japonica extract of the present invention may relax blood vessels. In addition, by hydrolyzing the extract of Wuchulchia japonica according to the present invention by enzymatic reaction, the content of L-arginine in the Wuchu wood is increased to increase the useful ingredient of the Wuchuchu tree extract and thereby improve the vasodilatory effect . Through this, it can be used for prevention, treatment or improvement of vascular disorder diseases caused by contraction of blood vessels. Examples of the vascular disorder diseases include hypertension, atherosclerosis, (peripheral) blood circulation disorder, vascular stenosis, stroke, cerebral infarction, cerebral hemorrhage, angina pectoris, myocardial infarction or ischemic brain disease.

The composition of the present invention comprising the extract of Tochigi or the hydrolyzate thereof may be prepared as a pharmaceutical preparation. The pharmaceutical preparations of the present invention can be prepared by using at least one selected from the group consisting of pharmaceutically acceptable carriers, diluents and excipients according to a method which can be easily carried out by those having ordinary skill in the art to which the present invention belongs. Or by formulating it into a unit dose form or by inserting it into a multi-dose container. The formulations may be in the form of solutions, suspensions or emulsions in oils or aqueous media, or in the form of excipients, powders, granules, tablets or capsules. The formulation may further comprise a dispersant or stabilizer.

If desired, the pharmaceutical preparation may further comprise a pharmaceutically acceptable carrier. Such pharmaceutically acceptable carriers are those conventionally used in the field of the present invention and include for example lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, calcium silicate, But are not limited to, crystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methylcellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

If desired, the pharmaceutical preparations of the present invention may further contain additives known in the art in addition to the above components. For example, it may further include at least one selected from the group consisting of a lubricant, a wetting agent, a sweetener, a flavoring agent, an emulsifying agent, a suspending agent, and a preservative agent, but is not limited thereto.

The pharmaceutical preparation of the present invention can be administered orally or parenterally. In case of parenteral administration, it can be administered by skin application, rectal injection, intravenous injection, subcutaneous injection, muscle injection, intraperitoneal injection and transdermal administration. A suitable dosage of the pharmaceutical composition of the present invention may be controlled by such factors as the formulation method, the manner of administration, the age, body weight, sex, pathological condition, food, administration time, administration route, excretion rate and responsiveness of the patient And the ordinarily skilled physician can readily determine and prescribe dosages effective for the desired treatment or prophylaxis. The daily dosage of the pharmaceutical composition of the present invention may be 0.001 mg / kg to 10 g / kg, preferably 1 mg / kg to 1 g / kg. If necessary, the above dose may be divided into several times and administered at predetermined time intervals. The daily dose of the pharmaceutical composition of the present invention can be adjusted by a skilled physician.

The composition comprising the extract of Hokkaido extract or hydrolyzate thereof of the present invention can be produced as a functional food. The functional food is a food prepared by adding the extract of Huangchu tree or its hydrolyzate to a food material, or a food prepared by extracting the Huangchu tree extract or a hydrolyzate thereof in capsules, powders, suspensions, etc., ≪ RTI ID = 0.0 > health food. ≪ / RTI > Examples of the food include drink, meat, sausage, bread, biscuit, rice cake, chocolate, candy, snack, confection, pizza, noodle, gum, ice cream, soup, beverage, tea, vitamin complex But is not limited thereto.

If necessary, the functional food of the present invention may further comprise components that are ordinarily added in food production. For example, there may be mentioned nutrients, vitamins, minerals (electrolytes), flavors, coloring agents, thickening agents, pectic acid, pectate salts, alginic acid, alginates, organic acids, protective colloid thickening agents, pH adjusting agents, stabilizers, preservatives, , Carbonating agent, pulp, and the like, but is not limited thereto.

In one embodiment of the present invention, the functional food may be a drink. The drink may further contain flavors or natural carbohydrates. The natural carbohydrate may be a monosaccharide (e.g., glucose, fructose, etc.); Disaccharides (e.g., maltose, sucrose, etc.); oligosaccharide; Polysaccharides (e.g., dextrin, cyclodextrin and the like); And sugar alcohols (e.g., xylitol, sorbitol, erythritol, etc.). Examples of the flavoring agent include natural flavoring agents (e.g., tau Martin and stevia extract) and synthetic flavoring agents (e.g., saccharin, aspartame, etc.), alone or in combination.

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in more detail with reference to the following examples. It will be apparent to those skilled in the art that these embodiments are illustrative of the present invention and are not intended to limit the scope of the appended claims and that various changes and modifications may be made to the embodiments within the scope and spirit of the invention , And it is natural that such variations and modifications fall within the scope of the appended claims.

Example

≪ Preparation of an extract of Wuchulia chinensis>

Leaf to the green part within 50cm from the end of the leaves was cut into 2㎝ of the raw material for extraction and hot air dried. Extracted water was added to 1kg of dried leaves of Hwacheon - gil, and dried at 100 ℃ for 4 hours. After the extraction, the concentrate was concentrated to a minimum concentration of 30 Brix and then lyophilized to obtain a solid form of the extract of Hwangchuogi extract. The yield was 20.9% (w / w).

≪ Preparation of Hydrolysis Extract of Wild Grass Tree >

Protein hydrolyzate was added to the hydrothermal extract of Hwangcholgak tree. 1g of the protease derived from Bacillus subtilis was treated and the enzyme reaction was carried out at 40 ° C for 4 hours. 1 g of an enzyme mixture in which trypsin and chymotrypsin were mixed at a weight ratio of 1: 1 was mixed with a protease derived from Bacillus subtilis. Next, two mixed peptide degrading enzymes were secondarily treated to a woodchuck extract. 1 g of bromelain and papain were each treated with the peptide decomposing enzyme for 16 hours at a temperature of 50 캜. And 1 g of pyrethroid were treated together to measure the amino acid production efficiency. Next, heat treatment was carried out at 100 ° C for 30 minutes, and hydrolysates of the extracts of Hwangchulchu tree, which had been finally arginine amplified, were prepared through a filter. The hydrolysates of Hwacheonchu extract were concentrated to a minimum concentration of 30 Brix.

<Measurement of Vasodilatory Effects of Extracts and Hydrolysates of Wild-tree Trees>

Sprague-Dawley rats (Samtako, Korea) at 200-300 g were admitted to a feeding environment with sufficient feed of solid feed (LabDiet 5L79, Orient Bio, Korea) and water Respectively. The mice were stunned and immediately bled, followed by a laparotomy along the abdominal centrometry and a thoracic aorta. The thoracic aorta was cut into rings of about 2 to 3 mm in length, Krabs solution (Krebs buffer (mM / L); 118.4 NaCl, 25 NaHCO ₃ , 11.66 glucose, 4.75 KCl, 1.18 MgSO ₄ .7H ₂ O, 2.5 CaCl ₂ .2H ₂ O, 1.19 KH ₂ PO ₄ , 0.02 EDTA, pH 7.4). While the oxygen was continuously supplied, the surrounding adipose tissue and connective tissue were cleanly removed, and then transversally cut to a length of about 2 to 3 mm to prepare a ring section.

To investigate the effects of Hwangchu - wood extracts and hydrolyzate of Hwangryeok tree on the relaxation of rat thoracic aortic vascular tissues, we first measured the functional activities of vascular aortic vascular tissues in the rat. The solution in the organ chamber maintained aeration at 95% oxygen (O ₂ ) -5% carbon dioxide (CO ₂ ) mixture at 37 ° C, pH 7.4. Tension of the blood vessels was measured using a polygraph system (PowerLab 8/35, AD Instruments, Dunedin, New Zealand) connected to an isometric transducer (MLT0201, Panlab, Cornella, Spain) and a computer analyzer Pro V8-MLS260 / 8, ADInstruments, Dunedin, New Zealand). Before the drug experiment, the thoracic aortic blood vessels underwent baseline tension by applying 1.5 g of force to the blood vessels, hanging one side of the vascular tissue to the lower side of the fascia and hanging the other side on a force-displacement transducer. After keeping the equilibrium equilibrium, Phenylephrine 10 ^-5 M, which is a vasoconstrictor, was administered and then the acetylcholine 10 ^{- 5} M, 10 ^{- 4} M, 10 M was added to the contracted aorta. ^It was confirmed that the addition of ^-3 M completely relaxed. After shrinking with Phenylephrine 10 ^-5 M, it was confirmed that the reaction was stable when exposed to the Krabs solution, and it was confirmed that the functional activity could be determined. The results of measuring the functional activity of vascular tissues are shown in Fig.

The rat chest of the effect of contracting the aorta vascular tissue confirmed phenyl LES principal (Phenylephrine) 10 ^{- 5} after treatment with M levels by inducing vasoconstriction, the hwangchil wood extract to the contracted blood vessel and administered in 10, 30μg / ml The degree of relaxation was extracted and the results are shown in Fig. The degree of relaxation was measured from the baseline to the degree of contraction by phenylephrine treatment, and the degree of relaxation resulting from administration of the extract was determined by the ratio.

FIG. 3 shows that the degree of relaxation of vascular smooth muscle is 40% and 50%, respectively, when the extract is injected.

Next, similarly, phenylephrine was administered to constrict the aorta, and the degree of relaxation of the contracted blood vessels was extracted by administering the hydrolyzed extract of Hwangryeok tree at 10, 30 / / ml. The results are shown in Fig.

FIG. 4 shows that the degree of vascular relaxation was 84% and 96%, respectively, when the hydrolyzed extract of Hwangryeok tree was administered.

<Animal model of hypertension model of extracts and hydrolysates of Hwangchil tree>

Experimental animals were purchased from Halran (Indianapolis, Ind., USA) with a specific pathogen free (SPF) condition of 250 ± 10 g for 7 weeks of age, male SHR and Wistar rats (WKY). After 1 week of preliminary feeding period, the mice were adapted to blood pressure measurement once a week in a calibration frame in a 37 ° C heating chamber, and then 45 male SHRs expressing hypertension were selected and grouped as 'Z' , And weighed using a digital meter at a certain time a week. Feedstuffs were freely infused with animal feedstuffs (Cargill Agri Purina, Inc., Seongnam, Korea), filters, and ultrafiltered sterile filtered water. Experimental animals were kept at 12 ± 12 ° C and humidity of 50 ± 5%. Wheatgrass extract or hydrolyzate was orally administered at daily concentration and systolic blood pressure was measured once a week during the experiment. In order to reduce the error range of the blood pressure measurement, the animals were fixed in a holder of a blood pressure analyzer (BP-2000 blood pressure analysis system, rat platform 2-channel, Visitech Systems, Apex, NC, USA) The blood pressure was measured three times repeatedly.

After 8 weeks of administration, all experimental animals were fasted for 12 hours and blood was collected from the large vena cava after anesthesia. The blood was centrifuged at 3,000 rpm at 4 ° C for 15 minutes to isolate the plasma. The plasma was separated by ACE (rat ACE ELISA kit, CUSABIO, Newark, DE, USA) and C-reactive protein (CRP, rat CRP ELISA kit, ALPCO, Salem, NH, USA) was measured at 450 nm absorbance.

Blood pressure and biochemical factors such as ACE and CRP of SHR, congenital hypertensive rats, were significantly increased compared with Wister rats.

Claims (9)

Dendropanax Morbifera ) or a hydrolyzate thereof as an active ingredient.
The method according to claim 1,
Wherein the hydrolyzate comprises an enzymatic treatment step of treating proteolytic enzyme in the extract of Hwangchujang; And
And a deactivation step of inactivating the treated enzyme. The composition for preventing or treating vascular diseases according to claim 1,
3. The method of claim 2,
The enzymatic treatment step may include a first step of treating Bacillus s ubtilis- derived protease, trypsin and chymotrypsin; And
A method for preventing or treating vascular diseases, comprising the step of treating bromelain and papain.
The method of claim 3,
Wherein the pepsin is further treated in the first step.
The method of claim 3,
Wherein the ficin is further treated in the second step.
The method according to claim 1,
Wherein the vascular disease is selected from the group consisting of hypertension, atherosclerosis, peripheral blood circulation disorder, vascular stenosis, cerebral infarction, angina pectoris, myocardial infarction and ischemic brain disease.
The method according to claim 1,
A composition for preventing or treating a vascular disease, wherein the extract is a vasoconstrictor.
Dendropanax Morbifera extract or a hydrolyzate thereof as an active ingredient.
Dendropanax Morbifera ) or a hydrolyzate thereof as an active ingredient.

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