KR20110081007A - Composition for preventing or improving hypertension containing fermented salicornia herbacea - Google Patents

Abstract

PURPOSE: A composition containing Salicornia herbacea fermentation is provided to ensure excellent antioxidation and to suppress angiotensin conversion enzyme. CONSTITUTION: A composition for preventing or treating hypertension contains Salicornia herbacea fermentation. A method for preparing the composition comprises: a step of adding hexane or butanol to Salicornia herbacea fermentation for demarcation; a step of adding sugar and fermenting for 45-51 months; a step of adding water to the Salicornia herbacea fermentation to prepare suspension; and a step of adding hexane or butanol.

Description

Composition for preventing or improving hypertension, including seaweed fermented products {COMPOSITION FOR PREVENTING OR IMPROVING HYPERTENSION CONTAINING FERMENTED SALICORNIA HERBACEA}

The present invention relates to a composition having a therapeutic, ameliorating or prophylactic effect on cardiovascular diseases, which comprises a seaweed fermented product as an active ingredient.

Most organisms are subjected to various environmental stresses caused by biological stresses such as germs, pests or viruses, or deterioration of the global environment. When a variety of stresses are applied to an organism, oxygen, which is essential for life, is highly reactive, causing an excessive increase in reactive oxygen species (ROS), which causes serious physiological disorders. The excess reactive oxygen species is recognized to be a cause for promoting aging, and has been reported to cause a variety of diseases.

Specifically, the reactive oxygen species or free radicals destroy cells, cut off the connective tissue of the dermal layer of the skin, or cause cross-linking, thereby causing skin-related abnormalities such as wrinkles, atopic dermatitis, acne or skin cancer, as well as cancer and myocardial infarction. cardiovascular diseases, including myocardial infarction, stroke, and atherosclerosis, and degenerative neurological diseases such as amyotrophic laternal sclerosis or Parkinson's disease (PD) It has been reported to cause various diseases such as chronic neurodegenerative disease) and rheumatoid arthritis.

In addition, reactive oxygen species can produce a harmful substance called lipid peroxide by peroxidating lipids in the human body, and the lipid peroxide acts on blood vessels and causes various adult diseases such as arteriosclerosis and blood serum.

It is a system that removes these active oxygen species in the living body, such as superoxide dismutase (SOD, EC 1. 15. 1.1), peroxidase (POD), catalase (CAT), etc. Polymeric antioxidant enzymes and antioxidants such as vitamin C, vitamin E or glutathione.

However, due to pollution, ultraviolet rays or various causes including the biological stress and aging, the antioxidant system of the human body gradually becomes unable to operate normally, and in this case, the active oxygen species can be removed to protect by ingesting antioxidants. There is a need for an in vivo supply of a substance that is capable of antioxidants.

Conventionally, synthetic antioxidants having excellent antioxidant power have been reported, such as butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT) or tertiary butylhydropuinone (TBHQ).

However, the synthetic antioxidants are toxic to some of the absorbent substances in the body, can be teratogenic factors and carcinogens (Ito, et al ., 1983), which may cause hepatomegaly or increase microsomal enzyme activity in the liver, and cause pathological damage to organ tissues such as lungs and kidneys (Branen, 1975). Is being raised.

Therefore, in recent years, many studies have been conducted to develop an antioxidant that is safer to the human body and excellent in antioxidant power. As part of this research, many studies on natural antioxidants are underway. More specifically, with the growing awareness of modern people's safety and health needs, natural antioxidants have been accumulating, as studies have reported that food intake, including natural antioxidants, can reduce the incidence of diseases caused by reactive oxygen species. There is a growing interest in.

As a result of continuous research on natural antioxidants such as searching for antioxidant effects on natural plants, many natural antioxidant components have been reported.

Natural antioxidants reported to date include antioxidants such as flavono derivatives, isoflavones, isoflavones, phenolic acids, tocopherols, saponins or trypsin inhibitors. Reported by Hayes et al ., 1977).

Along with these findings, studies on natural extracts containing high amounts of antioxidants or excellent anti-oxidant properties, which can be used as foods or included in foods, for the prevention of diseases caused by reactive oxygen species and prevention of aging Or the demand for development is increasing.

Angiotensin converting enzymes are dicarboxyl peptides found in the proximal tubules of the blood vessels and kidneys, endothelial, heart, lung, activated macrophages, and brain tissues. They are renin-angiotensin system, which regulates blood pressure and water balance in mammals, by renin. It is an enzyme that converts angiotensin I activated from angiotensinogen to angiotensin II. Angiotensin II acts on four types of AT receptors in the adrenal glands, vascular smooth muscle cells, kidneys, or heart. They cause vasoconstriction, release of aldosterone and vasopressin, tubular sodium absorption, and decreased blood flow to the kidneys. It is reported that this can lead to various lesions in the cardiovascular, renal and central nervous areas.

Therefore, angiotensin converting enzyme inhibitors or angiotensin converting enzyme inhibitors (ACE inhibitors) are reported to be able to treat or prevent cardiovascular diseases such as hypertension, heart disease, arteriosclerosis, or cerebral hemorrhage or kidney disease, and many studies have been conducted. It's going on. Specifically, the results of various clinical studies and clinical trials confirming that it can effectively reduce chronic kidney disease, arteriosclerosis, heart attack and death thereof are reported.

Based on these results now, chemically synthesized such as ramipril, captopril, enalapil, lisinopril, fosinoril or spirapril, etc. Many angiotensin converting enzyme inhibitors are used to treat hypertension. However, these compounds are easily degraded in pharmaceutical dosage forms, which means they are not stable and act on other cells, causing problems with side effects such as weakness throughout the body, vomiting, coughing, headache, anorexia, and taste disorders. It is reported to be.

In order to solve this problem, there is an urgent need to develop an angiotensin converting enzyme inhibitor derived from a natural substance which does not cause side effects and ensures safety. In particular, in the case of an angiotensin converting enzyme inhibitor derived from a natural product used as a food, it is easy to ensure safety, the need for research on this is increasing.

In order to meet the above demands, the present invention effectively inhibits angiotensin converting enzyme, which is useful for the treatment, prevention, or improvement of hypertension, and does not cause side effects, including natural plants that can be used for food, and is excellent in safety. The purpose is to provide.

In order to achieve the above object, the present invention provides a composition for the treatment or prevention of cardiovascular diseases, which can effectively inhibit angiotensin converting enzymes, as well as containing natural seaweed fermented fermented products without any side effects as an active ingredient. do.

In another aspect, the present invention provides a food composition for improving or preventing cardiovascular disease, including a seaweed fermented product as an active ingredient.

The present inventors have been investigating the pharmacological effects of natural plant-derived compositions, taking note that, in the case of natural plants used as foods, the possibility of safety related side effects or resistance is much less than that of conventional chemically synthesized drugs. , The fermented seaweed fermented by free radical scavenging activity, specifically through DPPH and ABTS radical scavenging activity, the antioxidant activity was excellent, and confirmed through the inhibitory activity of angiotensin converting enzyme, it was confirmed that the antihypertensive effect is excellent, it is effective The pharmaceutical composition comprising as a component has completed the present invention by confirming that it can treat, prevent or improve cardiovascular diseases.

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

The present invention relates to a composition for the treatment or prophylaxis of cardiovascular diseases, which comprises a seaweed fermented product as an active ingredient.

In the present invention, Salicornia herbacea is a perennial herb belonging to the family of the family Dwarf , it is also referred to as tongsu. The seaweeds are distributed in Korea, especially on the west coast of Korea, Japan, China, and India, and mainly grow in the seaside, in particular, near tidal flats where seawater enters or in inland salt basins. Stems are fleshy, cylindrical, branched, degenerate scales facing each other, and nodes stick out, which is why they are called spurs. Flowers bloom green in August-September and hang in three recesses between upper nodes of branches. Fruits are red, green, reddish purple in autumn, flat egg shape, ripen in October, covered with bark, and contain black seeds.

The seaweed may be collected in the Jeollanam-do, specifically Jeollanam-do tidal flat area, and collected in October, for example, and washed with running water to remove the tidal flat or foreign matter.

The seaweed fermentation product may preferably be a seaweed sugar fermentation product. The persimmon sugar fermentation product may be a fermentation product by the sugar fermentation method of the persimmon, specifically, after storing the persimmon in a sugar storage method, it can be prepared by performing a fermentation process.

Sugar storage method refers to a typical food storage method along with salting method or acid storage method, and refers to a method of marinating sugar. Specifically, the concentration of sugar or sugar in the whole food or composition is maintained at least 50% (w / w) to mold the food. B means a method of preventing corruption by inhibiting the growth of bacteria and the like. Generally, it can be used to make jam, jelly or sweetened condensed milk.

Fertilizer fermentation of the present invention, for example, can be prepared by mixing the washed with the seaweed and sugar, fermentation at 10 to 30 ℃. The seaweed and sugar may be mixed in a mixing ratio of 1: 1 (w / w) to 0.9: 1.1 (w / w), preferably 1: 1 (w / w) based on the weight ratio, and the fermentation may be The mixture of seaweed and sugar is placed in a fermentation vessel and sealed, and then fermented at 10 to 30 ° C., preferably at 20 to 27 ° C., more preferably at 25 ° C. for 45 to 51 months, preferably 47 to 49 months. It can manufacture. Since the growth of useful microorganisms is less than 10 ° C., the fermentation does not proceed, and at a temperature higher than 30 ° C., the growth of microorganisms may occur too much or there may be a microbial growth disorder due to high temperature. To 30 ° C. In addition, the fermentation period may be 45 months to 51 months, preferably 47 months to 49 months so that sufficient fermentation occurs at the fermentation temperature of the present invention, so that the original functionality of the seaweeds can be further enhanced. In the fermentation step, for example, the mixture of seaweed and sugar mixed with a mixture ratio of 1: 1 (w / w) based on the weight ratio of the seaweed and sugar packed in a fermentation vessel and sealed and fermented for 1 year at 25 ℃ 1 Preparing a step fermentation product; Removing the insoluble material in the first step of the fermentation and the first step of removing the insoluble material in the fermentation vessel may be sealed and then fermented for 3 years at 25 ℃.

As an example of the present invention, the fermented soybean paste contains the mixture of seaweed and sugar mixed in a mixture ratio of 1: 1 (w / w) based on the weight ratio of sugar and sugar in a fermentation vessel and then sealed at 25 ℃ 1 Fermentation for a year to produce a first stage fermented product; It can be prepared by a method comprising the step of removing the insoluble material in the first-stage fermentation and sealing the first-stage fermentation removes the insoluble material in a fermentation vessel and then fermented for 3 years at 25 ℃.

The seaweed fermentation may be preferably a fraction of the seaweed fermentation, more preferably a persimmon sugar fermentation fraction. The persimmon sugar fermentation fraction means a fraction of the persimmon sugar fermentation.

Fractions of the seaweed fermentation may be prepared by fractionation using the fraction solvent to the seaweed fermentation.

The fractional solvent may be water, a polar organic solvent, a nonpolar organic solvent or a mixed solvent thereof. The polar organic solvent may be an alcohol having 1 to 5 carbon atoms such as methanol, ethanol, ethyl acetate, acetone, and the like, and the nonpolar organic solvent may be hexane, chloroform, methylene chloride or dichloromethane. The fractional solvent may preferably be at least one selected from the group consisting of hexane, chloroform and butanol, and more preferably at least one selected from the group consisting of hexane and butanol. The fractional solvent may be added in an amount of 1: 0.1 (fermented product: fractional solvent) to 1:10 (fermented product: fractional solvent) based on a volume ratio with respect to the fermentation product or diluent (diluent) of the fermentation product.

The fraction may be prepared by adding and distributing one or more solvents selected from the group consisting of hexane and butanol. For example, the fraction may be prepared by adding water to the fermented fermentation of the seaweed to prepare a suspension, and then fractionating by sequentially adding hexane, chloroform, ethyl acetate and butanol, and the fraction may be performed by a distribution method.

Fractions of the fermentation may be prepared by performing a filtration process or the concentration and / or lyophilization for the fraction prepared by performing the fractionation process. By performing the filtration process it is possible to remove the residues and the like remaining in the fractionation liquid, it is possible to remove the fraction solvent by performing the concentration and / or lyophilization. In addition, the concentration may be carried out using a vacuum concentrator, the vacuum concentration process may be carried out under the conditions of 30 to 70 ℃, preferably 40 to 50 ℃.

The fractions of the fermentation product were added to the fermentation product or the fermentation product by diluting the diluted solution with hexane, chloroform, ethyl acetate and butanol in order to obtain a fraction solution for each fraction solvent, and then distilling the fraction solution under reduced pressure. It can be prepared by concentration.

In one embodiment of the present invention, the fermentation fraction of the persimmon seaweed is added to the sugar and fermented for 45 months to 51 months to prepare a fermentation of seaweed; And it may be prepared by a method comprising a fractionation step of fractionating by adding hexane or butanol to the fermentation and performing a distribution process. When dilution by adding water to the fermentation, the fermentation fraction of the seaweed is added to the sugar and fermented for 45 months to 51 months to prepare a seaweed fermentation; Preparing a suspension by adding water to the seaweed fermentation; And it may be prepared by a method comprising a fractionation step of fractionating by adding hexane or butanol to the suspension and performing a distribution process.

In addition, the obtained fractions can be stored in a deep freezer until use. In addition, the fraction may be a solvent obtained by completely removing the solvent through the concentration and the freeze-dried fraction obtained, the solvent is completely removed from the fraction used in the form of a powder or the fraction solvent used to prepare the fraction Can be used after being dissolved in distilled water or a common solvent.

Seaweed fermentation or fractions of the seaweed fermentation according to the present invention is excellent in antioxidant activity, not only excellent inhibitory ability of angiotensin converting enzyme, but also manufactured by using a natural plant that can be used for edible side effects such as safety and safety Since it is excellent, the seaweed fermentation or fractions of the seaweed fermentation may be used as an active ingredient of a pharmaceutical composition for the treatment or prevention of cardiovascular diseases or an active ingredient of a food composition for the improvement and / or prevention of cardiovascular diseases.

The fermented fermented soybean or fractions of the fermented soybean fermentation can be used as a composition for the treatment, prevention or improvement of cardiovascular diseases by inhibiting angiotensin converting enzyme, as well as excellent antioxidant activity and can inhibit angiotensin converting enzyme. In relation to the treatment, prevention or amelioration function of the cardiovascular disease, the fraction of the perilla fermentation may be preferably prepared using hexane or butanol as a fractional solvent.

In the present invention, the cardiovascular disease is a disease including heart disease and vascular disease, in the crowd consisting of hypertension, hypertensive heart disease, heart disease, arrhythmia, stroke, thrombosis, angina pectoris, heart failure, myocardial infarction, atherosclerosis and arteriosclerosis It may be any one selected, preferably hypertension or hypertensive heart disease.

Angiotensin converting enzymes are one of the dicarboxyl peptides found in the proximal tubules of the vessels and kidneys, endothelial, heart, lung, activated macrophages, and brain tissues. Angiotensin II is a group of four species found in the adrenal glands, vascular smooth muscle cells, kidneys, and heart. Acts on the AT receptor and causes various lesions in the cardiovascular, renal and central nervous areas by inducing vasoconstriction, release of aldosterone and vasopressin, absorption of sodium in the tubules and decreased blood flow to the kidneys It is reported to be importable. Therefore, the angiotensin converting enzyme inhibitor or angiotensin converting enzyme inhibitor (ACE inhibitor) is reported to be able to treat or prevent cardiovascular diseases such as hypertension, heart disease, arteriosclerosis, or cerebral hemorrhage or kidney disease, and specifically, clinical studies In clinical trials, angiotensin converting enzyme inhibitors have been reported to effectively reduce hypertension, chronic kidney disease, atherosclerosis, heart attacks and death.

Blood pressure in the present invention refers to the force that blood exerts on the walls of blood vessels. When reading blood pressure, it is divided into systolic blood pressure (highest blood pressure) and diastolic blood pressure (lowest blood pressure). Systolic blood pressure is the pressure exerted on blood vessels as the heart contracts and releases blood, while diastolic blood pressure is the pressure the blood vessel receives when the heart receives blood as it expands (relaxes).

The hypertension is a disease in which systolic blood pressure is 140 mmHg or more or diastolic blood pressure is 90 mmHg or more in adults over 18 years of age, and the cause is not found in cases of essential (primary) hypertension and the cause of which hypertension occurs. About 95% of all hypertensive patients are essential hypertension. Diseases caused by the hypertension include hypertensive heart disease (hypertensive heart disease).

The arteriosclerosis refers to a disease in which the walls of the arteries become thick and the elasticity of the arteries is reduced. When the atherosclerosis develops, the blood supply to the organs that received the blood from the hardened arteries is reduced, so that additional diseases may develop. An example of a typical disease related to this is coronary artery disease in which atherosclerosis changes in the coronary arteries that supply blood to the muscles of the heart.

The seaweed fermented product or the fraction of the seaweed fermented product effectively inhibits angiotensin converting enzyme, thereby treating, preventing or improving cardiovascular diseases such as hypertension and heart disease, arteriosclerosis or cerebral hemorrhage.

The composition for the treatment or prevention of cardiovascular diseases comprising the seaweed fermentation or fractions of the seaweed fermentation as an active ingredient can be directly applied to animals including humans. The animal is a biological group corresponding to plants, and mainly refers to the ingestion of organic matter as nutrients, digestion, excretion, and respiratory organs are differentiated, preferably mammals, and more preferably humans.

The composition for the treatment or prevention of cardiovascular diseases, comprising the seaweed fermentation or fractions of the seaweed fermentation of the present invention as an active ingredient may include only a seaweed fermentation or a fraction of the seaweed fermentation, other formulations, methods and uses It may further comprise a pharmaceutically acceptable carrier, excipient or diluent depending on the purpose.

When provided with a mixture containing other ingredients in addition to the seaweed fermentation or the fraction of the seaweed fermentation as an active ingredient to the composition for the treatment or prevention of cardiovascular diseases comprising the seaweed fermentation or fractions of the seaweed fermentation as an active ingredient , 0.001% by weight to 99.9% by weight, based on the total weight of the composition for the treatment or prevention of cardiovascular diseases, including the seaweed fermentation or fractions of the seaweed fermentation as an active ingredient Preferably from 0.1 wt% to 99 wt%, more preferably from 1 wt% to 50 wt%.

When the composition for the treatment or prevention of cardiovascular diseases, including the seaweed fermentation or fractions of the seaweed fermentation as an active ingredient is used as a medicament, the administration method can be oral or parenteral, for example, oral, transdermal, subcutaneous It can be administered via several routes including intravenous or intramuscular.

In addition, the formulation of the composition may vary depending on the method of use and may be formulated by employing methods known in the art to provide rapid, sustained or delayed release of the active ingredient after administration to a mammal. Can be.

Generally, solid preparations for oral administration include tablets, pills, soft or hard capsules (CAPSULES), pills (PILLS), powders (POWDERS) and granules (GRANULES), and the like. Excipients, for example, may be prepared by mixing starch, calcium carbonate, sucrose or lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Liquid preparations for oral use include suspensions, liquids, limonades, emulsions, and syrups. In addition to commonly used simple diluents such as water and liquid paraffin, Excipients such as wetting agents, sweetening agents, fragrances, preservatives and the like can be included.

In addition, for parenteral administration, creams, lotions, creams, ointments, eye creams, warnings, liquids, aerosols, fluids, etc. (FRUIDEXTRACTS), ELIXIR, INFUSIONS, SACHET, LINIMENTS, PATCH or INJECTIONS.

Furthermore, the compositions of the present invention may be formulated using suitable methods known in the art or using methods disclosed in Remington's Pharmaceutical Science (Recent Edition, Mack Publishing Company, Easton PA). Can be.

Pharmaceutically acceptable carriers, excipients or diluents according to the formulation, method of use and purpose of use are lactose, dextrose, sucrose, sorbitol, mannitol, xyitol, erythritol, maltitol, starch, akicia rubber, alginate, gelatin, calcium Phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, dextrin, calcium carbonate, Propylene glycol, liquid paraffin, may be one or more selected from the group consisting of physiological saline, but is not limited thereto, conventional carriers, excipients or diluents can be used.

In addition, when pharmaceuticalizing a composition for the treatment or prevention of cardiovascular diseases, including the seaweed fermentation or fractions of the seaweed fermentation as an active ingredient, conventional fillers, extenders, binders, disintegrants, surfactants, anticoagulants, lubricants , Wetting agents, fragrances, emulsifiers or preservatives may be further included, oral or parenteral can be used, but may be preferably used for oral administration. Specifically, solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and the solid preparations include at least one excipient such as starch, calcium carbonate, and sucrose in the extract. (sucrose), lactose (lactose), gelatin, etc. are mixed and prepared. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Liquid preparations for oral use include suspensions, solvents, emulsions, and serums.In addition to commonly used simple diluents such as water and liquid paraffin, various excipients include, for example, wetting agents, sweeteners, fragrances, and preservatives. Can be.

Dosage of the composition for the treatment or prevention of cardiovascular diseases comprising the seaweed fermentation product or the fraction of the seaweed fermentation according to the present invention as an active ingredient, the administration method, the age, sex and weight of the recipient, the severity of the disease, etc. It may be appropriately selected by those skilled in the art in consideration of the above. In one embodiment, the composition for the treatment or prevention of cardiovascular diseases comprising the fraction of the seaweed fermentation or the seaweed fermentation of the present invention as an active ingredient is the content of the daily active ingredient, that is, the fraction of the seaweed fermentation or the seaweed fermentation Based on the content of may be administered from 0.0001 mg / kg (body weight) to 1000 mg / kg (body weight), to be more effective from 0.01 mg / kg (body weight) to 100 mg / kg (body weight). Administration may be administered once a day or may be divided several times. The dosage does not limit the scope of the invention in any aspect.

In addition, the composition for the treatment or prophylaxis of cardiovascular diseases, comprising the persimmon fermentation product or a fraction of the persimmon fermentation of the present invention as an active ingredient, a compound or plant extract having a known antihypertensive effect, in addition to the fraction of the persimmon fermentation or persimmon fermentation It may further include, and may be included in 5 parts by weight to 20 parts by weight with respect to 100 parts by weight of the fertilizer.

In addition, the present invention relates to a food composition for improving or preventing cardiovascular diseases, which comprises a seaweed fermented product as an active ingredient. Examples of the food composition of the present invention include food, food additives, beverages or beverage additives.

Food composition for the improvement or prevention of cardiovascular diseases, including the seaweed fermentation or fractions of the seaweed fermentation as an active ingredient may further comprise suitable carriers, excipients and diluents commonly used in the preparation thereof.

In the present specification, the term "food" means a natural product or processed product containing one or more nutrients, and preferably means a state in which it can be directly eaten through some processing process. It is intended to include all foods, food additives, health functional foods and beverages.

Examples of the food that may contain the fermented fertilizer or fractions of the fermented soybean fermentation which are the active ingredients of the food composition of the present invention include various foods, beverages, gums, teas, vitamin complexes, functional foods, and the like. In addition, the food in the present invention includes special nutritional products (e.g., prepared oils, infants, baby food, etc.), processed meat products, fish products, tofu, jelly, noodles (e.g. ramen, noodles, etc.), health supplements, seasoned foods ( For example, soy sauce, miso, red pepper paste, mixed soy sauce), sauces, confectionery (e.g. snacks), dairy products (e.g. fermented milk, cheese, etc.), other processed foods, kimchi, pickles (various kimchi, pickles, etc.), beverages ( Examples include, but are not limited to, fruits, vegetable drinks, soy milk, fermented beverages, ice cream, etc., natural seasonings (eg, ramen soup, etc.), vitamin complexes, alcoholic beverages, alcoholic beverages, and other health supplements. The food, beverage or food additive may be prepared by a conventional production method.

Functional food in the present invention is the control of biological defense rhythm, disease prevention and recovery of food groups or food compositions that have added value to the food by using physical, biochemical, biotechnological techniques, etc. It refers to a food processed by designing so as to fully express the gymnastics function, and more specifically, the antihypertensive function in the living body. The functional food may include food acceptable food additives, and may further include appropriate carriers, excipients and diluents commonly used in the manufacture of functional foods.

In the present invention, the drink is a generic term for drinking to quench thirst or to enjoy the taste and is intended to include a functional drink. The beverage contains, as an essential ingredient, the fermented fermentation product or the fraction of the fermentation product as an active ingredient, and there are no special limitations on the other ingredients, and various flavors or natural carbohydrates are added as in general drinks. It may contain as a component. Examples of such natural carbohydrates include monosaccharides such as glucose, fructose and other disaccharides such as maltose, sucrose and the like and polysaccharides such as dextrin, cyclodextrin and the like, and Sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (tauumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The ratio of the natural carbohydrate may generally be about 1 to 20 g, preferably 5 to 12 g per 100 ml of the composition of the present invention. It may further contain a pulp for.

In addition to the above, the composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, coloring and neutralizing agents (such as cheese and chocolate), pectic acid and salts thereof, alginic acid and its Salts, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like. These components can be used independently or in combination. The additive may be 0 to 20 parts by weight, preferably 0.00001 to 15 parts by weight, per 100 parts by weight of the seaweed fermentation or the fraction of the seaweed fermentation as an active ingredient of the present invention, but is not limited thereto.

Functional beverage in the present invention is a biological defense rhythm control, disease prevention and the like having a beverage group or a beverage composition that has added value to the beverage by using physical, biochemical, biotechnological techniques, etc. to function and express the function of the beverage to a specific purpose Means a beverage that is designed and processed to fully express the gymnastics function related to recovery.

The functional beverage is not particularly limited to other ingredients except for containing the above-mentioned seaweed fermentation product or the fraction of the seaweed fermentation, which are the active ingredients of the present invention as essential ingredients in the indicated ratios, and various flavors or natural carbohydrates as in general beverages. Etc. can be contained as an additional component. Examples of such natural carbohydrates include monosaccharides such as glucose, fructose and other disaccharides such as maltose, sucrose and the like and polysaccharides such as dextrin, cyclodextrin and the like, and xylitol Sugar alcohols such as sorbitol and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (tauumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The natural carbohydrate may be included in an amount of 0 to 20 parts by weight, preferably 1 to 18 parts by weight, more preferably 5 to 12 parts by weight, per 100 parts by weight of the composition of the present invention.

In addition, in the food composition for improving or preventing cardiovascular diseases, including the seaweed fermentation or fractions of the seaweed fermentation as an active ingredient, the amount of the seaweed fermentation or the fraction of the seaweed fermentation is 0.00001% by weight of the total food weight It may be included in 50% by weight, the beverage composition may be included in a ratio of 0.001 g to 50 g, preferably 0.01 g to 10 g based on 100 ml of the total volume of the food, but is not limited thereto.

The composition of the present invention is excellent in antioxidant activity, and can inhibit angiotensin converting enzyme, which is helpful in the treatment, improvement or prevention of cardiovascular diseases including hypertension, and is manufactured from natural plants used for food. It is judged that it can be usefully used in patients with cardiovascular disease or patients at risk of the disease.

In addition, the present invention provides a method for producing a fraction of the seaweed fermentation having an effect of improving or preventing cardiovascular diseases.

Method for producing a fraction of the seaweed fermented product having an effect of improving or preventing the cardiovascular disease comprises a) a seaweed washing step of washing the seaweed with running water to remove tidal flats or foreign matter; b) mixing the washed seaweed and sugar at a weight ratio of 1: 1, the mixture is placed in a fermentation vessel and sealed, and fermented at 20 to 27 ° C., preferably at 25 ° C. for 1 year, to give a first-stage fermentation product. A step 1 fermentation step of preparing; c) removing the insoluble material from the first step fermentation, and then put in a fermentation vessel and sealed again and fermented at 20 to 27 ℃, preferably 25 ℃ for three years to prepare a two-stage fermentation step and d) after the addition of water to the two-stage fermentation to prepare a suspension, it may include the step of preparing a hexane fraction by the method of fractionating by adding hexane.

The persimmon sugar fermented hexane fraction or butanol fraction prepared by the above method is excellent in antioxidant activity and superior in angiotensin converting enzyme inhibitory activity compared to other fractions, and thus may be useful in patients with cardiovascular diseases or when there is such a risk. There is an advantage.

The composition comprising the seaweed fermentation or fractions of the seaweed fermentation of the present invention as an active ingredient is excellent in antioxidant activity and can inhibit angiotensin converting enzyme, which is effective in the treatment, improvement and prevention of cardiovascular diseases including hypertension, Unlike conventional medicines for treating high blood pressure, including artificial hypertension, which is mainly composed of artificial compounds, it is possible to treat, improve or prevent cardiovascular diseases by using substances derived from natural substances as active ingredients without causing side effects. It can be usefully used as a food composition or a medical composition for, and furthermore, because it is made from raw seaweed that is abundantly grown in the tidal flats of the west coast of Korea, in particular, the Jeollanam-do coastal area has the advantage of excellent economic efficiency. Therefore, the composition of the present invention can be widely used in related projects in that it can replace a substance for the treatment or amelioration of an existing chemically produced cardiovascular disease.

1 is a flow chart showing the fractionation process performed to prepare a fraction of the seaweed fermentation, according to an embodiment of the present invention.
Figure 2 is a graph comparing the inhibitory ability of Anjinotensin converting enzymes of the seaweed fermentation according to the fermentation period, according to an embodiment of the present invention, FG-02 represents a fermented seaweed fermented for two years, FG-04 is four years Fermented seaweed fermented products are shown, and FG-06 represents fermented soybean fermented products for 6 years.
Figure 3 is a graph comparing the angiotensin converting enzyme inhibitory ability of the fractions according to the type of fractional solvent in order to confirm the antihypertensive capacity of the fractions of the seaweed fermentation according to an embodiment of the present invention.
Figure 4 is a graph confirming the antioxidant capacity of the fractions of the fermented seaweed fermentation according to an embodiment of the present invention according to the type of fractional solvent, Figure 4a is a graph comparing the DPPH free radical scavenging ability of the fractions according to the type of fractional solvent , 4b is a graph comparing the ABTS radical scavenging ability of the fraction according to the fraction of the solvent.

Hereinafter, the preparation examples and examples are presented in order to explain the present invention in more detail. However, the following Preparation Examples and Examples are merely illustrated to aid the understanding of the present invention, and may be modified in various other forms, and the scope of the present invention is not limited to the following Examples.

Example 1 Preparation of Seaweed Fermentation and Seaweed Sugar Fermentation Fraction

The sea urchin ( Salicornia herbacea ) used in the present invention was inhabited in the native seagrass in Chonnam tidal flat in October. The fermented soybean paste of the present invention is fermented at room temperature for 2 years, 4 years or 6 years.

More specifically, the native seaweed was collected in October in Jeonnam tidal flat area, and then washed three times in clean water to remove the tidal flat or foreign matter. After the washing, 1 kg of dried seaweed was mixed with 1 kg of sugar, sealed in a fermentation vessel, and then fermented at 25 ° C. for 1 year. After 1 year, the fermented product fermented in the fermentation vessel, the insoluble seaweed was removed, the remaining fermentation broth was put in the fermentation vessel and sealed again, and then fermented and aged at 25 ° C. for 1 year, 3 years and 5 years.

Preparation of the fractions for the prepared persimmon sugar fermentation was carried out in the following manner for each solvent.

First, a suspension is prepared by adding 500 ml of water to 1,500 ml of the persimmon sugar fermentation broth fermented for 4 years, and then adding 2,000 ml of n-hexane to the suspension and partitioning to obtain a normal hexane layer. It was. After removing the normal hexane layer, 2,000 ml of chloroform (CHCl ₃ ) was added to the remaining aqueous layer and partitioned to obtain a chloroform layer. After removing the chloroform layer, 2,000 ml of ethyl acetate (ethyl acetate, EtOAc) was added to the remaining aqueous layer and partitioned to obtain an ethyl acetate layer. After removing the ethyl acetate layer, 1,000 ml of saturated normal butanol (n-butanol, BuOH) was added to the remaining aqueous layer and partitioned to obtain a normal butanol layer. The normal butanol layer was removed and the remaining aqueous solution was obtained as a water fraction layer.

The hexane fractionation layer, the chloroform fractionation layer, the ethyl acetate fractionation layer, the butanol fractionation layer and the water fractionation layer obtained by each of the fermentation broths and the fractional solvents of the fermentation broth according to the fermentation period were respectively cooled aspirators (CCA-1110, Eyela, Japan). Concentrated under reduced pressure at 40 ℃ using a vaccum evaporator equipped.

< Example   2> Hamcho Fermented  Antihypertensive activity OK1  -Activity according to fermentation period

The antihypertensive activity of the fermented soybean sugar fermentation broth fermented for 2, 4 and 6 years prepared in Example 1 was confirmed as an inhibitory activity against angiotensin converting enzyme (ACE). The inhibition of the ACE was measured by the following method.

First, 50 μL of the plasma, fermented to each concentration prepared in Example 1 and 100 μL of 0.1 M Sodium borate buffer containing 300 mM NaCl were mixed, and then 5 mM Hippuryl-histidyl-leucine. A solution was prepared by adding 50 μL of a solution (Hippuric acid-Histidine-Leucine). After the solution was reacted at 37 ° C. for 45 minutes, 200 μL of 1 N HCl was added thereto, and 2 mL of ethylacetate was added thereto. After addition, it was vortexed and centrifuged at 2,000 rpm for 5 minutes to take 1.5 mL of the supernatant. The solution taken was dried, 1 mL of 1 M NaCl was added and the absorbance was measured at 228 nm. From the measured absorbance results, the angiotensin converting enzyme activity was 100% when no fermentation was added, and the inhibitory activity was obtained by comparing the degree of inhibition when each fermentation was added. 2 is shown.

As shown in FIG. 2, it was confirmed that the fermented sugar fermented for 4 years had the best angiotensin converting enzyme inhibitory ability. In particular, sugar fermentation products fermented for 4 years at a concentration of 3 μL / mL to 5 μL / mL are superior to angiotensin converting enzyme inhibitor by about 20% or more than sugar fermentation products fermented for 2 years, and compared to sugar fermentation products fermented for 6 years. It was confirmed that the angiotensin converting enzyme inhibitory ability was about 10% or more. Angiotensin converting enzymes are enzymes located upstream of cardiovascular disease, especially in relation to elevated blood pressure, and at least 10% or 20% of the activity of these enzymes located downstream is downstream, In view of the suppression of blood pressure rise corresponding to the body phenomenon can be seen as a significant effect.

From the above results, it is understood that fermentation of the persimmon sugar fermentation is too short or too long in terms of antihypertensive ability, and the total fermentation period is preferably 4 years. Therefore, in the experiments on the following fractions, the experiment was performed on the sugar fermentation with a total fermentation period of 4 years.

<Example 3> Confirmation of antihypertensive activity of seaweed fermentation 2- Activity confirmation by fractional solvent

As confirmed in Example 2, the antihypertensive activity of the fourth-year sugar fermentation fraction prepared in Example 1 was confirmed as an inhibitory activity against angiotensin converting enzyme (ACE). The inhibition of the ACE was measured in the same manner as in Example 2.

The measured absorbance results were shown as the inhibitory ability of angiotensin converting enzyme by comparing the activity of the control group with distilled water instead of the sample and the measured activity, and the values comparing the angiotensin converting enzyme inhibitory activity of the respective fractions are shown in FIG. 3.

As shown in FIG. 3, the angiotensin converting enzyme inhibitory ability was the best in the hexane fractionation layer, and the butanol layer showed the high inhibitory ability. In addition, the water layer showed significantly lower inhibition. The best hexane fractionation layer showed about 10 times more inhibitory activity than the water fractionation layer, and showed about 150% inhibition ability compared to the ethyl acetate layer and the chloroform layer.

Example 4 Confirmation of Antioxidant Activity of Seaweed Ferment (Fragment)

Antioxidant activity of the persimmon sugar fermentation fraction prepared in Example 1 was confirmed by DPPH free radical scavenging ability and ABTS radical scavenging ability. The antioxidant activity was performed in the following manner, respectively.

The DPPH free radical scavenging ability was mixed lightly with a voltex mixer by adding 100 mM Tris-HCl buffer (pH 7.4, 400 μL) and 500 μM DPPH ethanol solution (final concentration 100 μM, 500 μL) to each fraction. The reaction was carried out for 30 minutes at. The absorbance of the reaction solution was measured at 517 nm using a spectrophotometer (UV-Visible, Varian) and the results are shown in Figure 4a.

In addition, ABTS radical scavenging ability was confirmed using the ABTS radical solution. The ABTS radical solution was mixed with 2.5 mM ABST dissolved in 1.0 mM 2,3'-azobis (2-amidino-propane) dihydrochloride (AAPH) in phosphate-buffered saline (PBS), and then 30 It was prepared by reacting for minutes. The PBS was a solvent containing 150 mM NaCl as 100 mM potassium phosphate buffer (pH 7.4). At this time, the concentration of the blue-green ABST radical was adjusted to be 0.7 ± 0.02 (mean ± SD) at 734 nm using a spectrophotometer. After mixing 20uL of each fraction and 980uL ABST radical solution, reacting for a certain time at 37 ℃, the degree of absorbance decrease at 734 nm was measured to investigate the ABST radical scavenging activity of the sample and the results are shown in Figure 4b Indicated. The control group mixed 20 uL of 100% methanol instead of the fractions.

As shown in FIG. 4, the hexane fractionation layer and the chloroform fractionation layer were found to have excellent antioxidant activity. More specifically, as shown in Figure 4a, the DPPH free radical scavenging ability was confirmed that the concentration-dependent increase in the hexane fraction layer, chloroform fraction layer and ethyl acetate layer, in particular the hexane fraction layer is the best, based on the final concentration It was confirmed that the antioxidant activity was about 1.5 times higher than that of the chloroform fractionation layer and about 2 times higher than the ethyl acetate fractionation layer. In addition, as shown in Figure 4b, in the case of ABST radical scavenging ability, the chloroform fractionation layer was the best, the hexane fractionation layer was confirmed to be the next excellent. The butanol fraction and the water fraction were very low in antioxidant activity. Compared with the ethyl acetate fraction, the hexane fraction was about 150% of the ethyl acetate fraction and about 200% in the chloroform fraction. It was confirmed that there is.

From the above results, it was confirmed that the hexane fraction layer and the chloroform fraction layer of the persimmon sugar fermentation were remarkably superior to the other fraction layers with antioxidant effects.

Claims (5)

A composition for the treatment or prevention of cardiovascular diseases, comprising a seaweed fermented product as an active ingredient. The method of claim 1,
The fertilizer fermentation is a composition for the treatment or prevention of cardiovascular diseases is a fermentation fractions fractions added by adding hexane or butanol to the fermentation. The method of claim 2,
The seaweed fermentation fraction is
Adding sugar to the seaweed and fermenting for 45 to 51 months to prepare a fermentation of seaweed; Preparing a suspension by adding water to the seaweed fermentation; And fractionation step of fractionating by adding hexane or butanol to the suspension and performing a distribution process.
Composition for the treatment or prevention of cardiovascular diseases, characterized in that it is prepared by a method comprising a. The method of claim 1,
The cardiovascular disease is a composition for the treatment or prevention of cardiovascular disease is any one selected from the group consisting of hypertension, hypertensive heart disease, heart disease, arrhythmia, stroke, thrombosis, angina pectoris, heart failure, myocardial infarction, atherosclerosis and arteriosclerosis. Food composition for the improvement or prevention of cardiovascular diseases, including a seaweed fermented product as an active ingredient.

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