KR20120001152A - Composition comprising deep sea water for preventing and treating obesity or hyperlipidemia and atherosclerotic-vascular diseases - Google Patents

Abstract

PURPOSE: A composition containing deep sea water is provided to reduce neutral fat, cholesterol, phospholipide, and hydroxyl radical and to prevent and treat obesity or hyperlipidemia. CONSTITUTION: A pharmaceutical composition for preventing and treating obesity or hyperlipidemia and arteriosclerotic vascular diseases contains deep sea water as an active ingredient. The deep sea water is collected under 300-1300m from East sea. The arteriosclerotic vascular diseases include artery scleroma, cardiac insufficiency, hypertensive heart disease, arrhythmia, congenital heart disease, myocardial infarction, angina, stroke, or peripheral vascular disease. A health food for preventing and treating obesity and arteriosclerotic vascular diseases contains the deep sea water as an active ingredient. The health food is powder, granule, tablet, capsule, or beverage.

Description

Composition comprising deep sea water for preventing and treating obesity or hyperlipidemia and atherosclerotic-vascular diseases}

The present invention relates to a composition for the prevention and treatment of obesity or hyperlipidemia and atherosclerotic vascular disease containing deep sea water as an active ingredient.

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43. Lowry O. H., Rosebrough. N. J., Farr, A. L., and Rardall, R. J.,: J. Biol. Chem., 193, 265 (1951)

44. Mc Growan M.w., Artiss J.D., Stramdbergh D.R., Aperoxid ase-coupled method for the colorimetric determination of serum triglycerides, Clin. Chem., 29, 538 (1983)

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46. Noma A., Matsushita S. Komori T .: High-density lipoprotein cholesterol levels of very old people in the diagnosis of dementia, Oxford Journals 15, 267-270 (1986)

Oyanagui, Y. Reevaluation of assay methods and establishment of kit for superoxide dismutase activity. Anal . Bioshem ., 142, 290-296 (1984)

48 Richmond W., Use of cholesterol oxidase for assay of total and free cholesterol in serum by continuous flow analysis, Clin. Chem., 22, 1579 (1976)

Yagi K .: Lipid peroxides and human diseases, Chemistry and Physics of Lipids 45, 337-342 (1987)

Disease is a part of human life, and its pattern has changed with age. The economic development and high industrialization, rapid population growth and densification, environmental and health hygiene, and the development of new therapies that our society has experienced over the past 100 years have changed the disease structure of our people more than ever before. Brought. Korea's disease structure is shifting from infectious diseases to adult diseases, and the morbidity and mortality levels are changing accordingly (Kiwan et al. In terms of sign structure of Koreans, tuberculosis, bronchitis, gastroenteritis, etc. occupied the upper ranks before the 1950s. However, in 1997, the number of signs of death was circulatory disease (hypertensive disease, cerebrovascular disease, ischemic heart disease). , Arteriosclerosis, etc., accounting for 23.4% of all deaths (Eun-Kyung Kim et al. 4, Life Cycle Nutrition. Shin-Kwang Publisher, 2005). Cardiovascular disease is a major cause of premature mortality worldwide and is a multifactorial disease caused by genetics and other environmental factors. It has been reported to be closely related to lipid nutrition (Cho Sung-Hee, Lipid and Arteriosclerosis, Korea Nutrition) Korean Journal of Food Science and Technology 23 (1) , pp.170-179, 1994; Korean Food Industry Association Food Research Institute, A Study on the Relationship between Nutrition and Special Diseases, 1988).

Hyperlipidemia is the case when the concentration of serum lipids is higher than normal (Illingworth, DR et al ,, Atherosclerosis, 4 , p. 270, 1984). These symptoms are due to increased synthesis of triglycerides in the small intestine and triglycerides in the liver. Increased synthesis, decreased HDL-cholesterol synthesis, increased VDL-cholesterol synthesis and secretion (Eddy, NB et al ,, Synthetic analgesics. II.Dithienylbutenyl- and dithienylbutylamines.J Pharmacol Exp Ther. 107 (3) , pp. 385 -393, 1953; D ^, Amour, FE, et al ,, A method for determining loss of pain sensation.J. Pharmacol.Exp. Ther. 72 , p.74, 1941; Imad Damaj, M. et al ,, , Tolerance to the antinoceptive effect of epibatine after acute and chronic administration in mice.Europian J Pharmacol. 300 , pp.51-57, 1996) or due to tissue damage following lipid peroxidation (Kim Song-jeon, Kim Man-soo.ω-3 Effects of Fatty Acids on Serum Lipids in Cholesterol-treated Rats, Journal of the Korean Chemical Society, 1991; Non-dependent effects the amount of fish oil administered in diabetic patients on serum lipids, Korea Nutrition Society, 26 (6), pp.672-679, 1993).

In hyperlipidemia, the major components of increased serum lipid components are composed of fat-soluble substances such as cholesterol, triglycerides, phospholipids, and free fatty acids, and hypercholesterinemia, depending on which of these lipid substances increases mainly. It is called hypertriglyceridemia. Increased serum cholesterol and triglycerides are the most common causes of hyperlipidemia. Accumulation of excess fat causes blood circulation disorders and microcirculation failure, resulting in atherosclerosis, ischemic heart disease, cerebral infarction, hypertension, obesity, diabetes, etc. (Schoen FJ et al., Robbins pathologic basis of disease, 5 th ed . , pp. 473-484, 1994).

Cholesterol is produced mainly in the liver and is present in the blood in the form of small round particles called lipoproteins, which carry cholesterol throughout the body. There are two types of lipoproteins, low density lipoprotein (LDL) and high density lipoprotein (HDL), and because high density lipoproteins carry cholesterol from other tissues to the liver, a lot of high density lipoproteins remove cholesterol from blood vessels. On the other hand, low-density lipoproteins are mainly produced by the liver and transport cholesterol to other tissues of the human body, so a lot of low-density lipoproteins accumulate a lot of cholesterol in blood vessels to promote arteriosclerosis, and about 70% of blood cholesterol is present as low-density lipoproteins, which are bad cholesterol.

In fact, cholesterol is an essential ingredient for normal functioning of the human body, a nutrient necessary for making cells, and a component of various hormones such as corticosteroids, male hormones, and female hormones. do. In addition, cholesterol is a nutrient necessary for the human body such as being used as a constituent of biological membranes and as a starting material for hormonal synthesis. However, excessive cholesterol intake is known to accumulate in the blood vessels and cause heart disease, and there is no preventive method except low-cholesterol diet, and taking drugs such as cholesterol-lowering drugs is effective. Use is extremely limited due to reasons such as causing side effects such as liver dysfunction.

Chitosan, phytosterol, inositol, pectin, etc. are known to lower blood cholesterol in the human body, but the effects and metabolic mechanisms are not clear when phytosterol is excluded. not. Phytosterol, a plant sterol due to its structural similarity to cholesterol, has already been identified as a mechanism for inhibiting cholesterol absorption metabolism in the body through competition with low-density lipoprotein-cholesterol, which is harmful to the human body. As a food additive, the US Food and Drug Administration (FDA) Has been approved.

Hyperlipidemia drugs are used to lower levels of excess blood lipids, especially cholesterol and triglycerides. Major drugs used in lipid metabolism include statins, bile acid blockers and fibric acid derivatives, each of which acts as a different mechanism. The choice of therapeutic agents for hyperlipidemia may be a combination of these drugs, depending on the type of lipoproteins that have been increased, and they require long-term oral daily use. These drugs effectively lower cholesterol and blood lipid levels, but have the disadvantage of having side effects. Statins can cause nausea, headache, abdominal pain and diarrhea or constipation, which can cause muscle inflammation, and bile acid blockers can reduce the intestinal absorption of vitamins A, D, and K. And fibric acid derivatives are unsuitable drugs for kidney disease, liver disease or gallbladder disease. Therefore, there is an increasing demand for the development of medicines and functional foods containing natural products to replace these preparations (Kook Seung-rae et al., 18 (3) , pp.317-327, 1997).

Atherosclerosis causes vascular diseases such as stroke and coronary artery disease. In particular, angina and acute myocardial infarction caused by coronary artery disease have increased significantly over the last 20-30 years due to rapid social and economic development and westernized lifestyle. Arteriosclerosis is the second most common circulatory disease after hypertension, and it is one of the most important diseases in national health, with cancer accounting for a large portion of deaths. Therefore, the importance of research on the pathogenesis and treatment of atherosclerosis is increasing.

There are many causes of atherosclerosis, but elevated plasma lipids, particularly plasma cholesterol and neutral lipids, are known as one of the most important risk factors.

Hyperlipidemia is an important risk factor for atherosclerosis and is a clinically important condition that causes major deaths such as ischemic heart disease and cerebrovascular disorders. Atherosclerosis prevention is known to be associated with improved lipid and hyperlipidemia.

The pathological model of experimental hyperlipidemia is divided into exogenous model and endogenous model. Exogenous hyperlipidemic condition models include hypercholesterolemia-induced models caused by high cholesterol dietary load, that is, hyperlipidemia by administration of vitamin D, cholesterol, olive oil, corn oil, etc., and endogenous hyperlipidemia models include fructose administration and WR. Models by administration of -1339 (Tripton WR-1339) (Ham IH et al., Kor. J, Herbology, 20 , pp. 45-52, 2005). Among them, Poloxamer 407 is an anesthetic emulsifier (Lee HH et al., Kor. J. Anesthesiol, 40 , pp. 515-521, 2001), poorly soluble drug solubilizer (Choi JY et al., J. Kor. Pharm. Sci., 18 , pp. 240-241, 1988), skin ointments (Kim KK et al., J. Kor. Pharm. Sci., 28 , pp. 15-23, 1998), and the like. However, when administered in humans, lipids are increased, and in particular, triglycerides are increased, causing hyperlipidemia. Free fatty acids are produced in adipocytes for at least 24 hours after poloxamer injection (Nash VJ et al., Pharmacotherapy, 16 , pp. 10-15, 1996), and the action of lipoprotein lipase (LPL) Decreases the rate of degradation of triglycerides that interfere with it (Stellato C. et al., Br. J. Anaesth., 67 , pp.751-758, 1991), and increases blood cholesterol and triglycerides in the liver. This is because it lowers the activity of hydroxy-3-methylglutaryl coenzyme A (HMG-CoA; 3-hydroxy-3-methylglutaryl CoA) (Wout GM et al., J. Paren. Sci. Technol., 46 , pp. 192-200, 1992).

Lipid peroxidation in the blood is known to cause cytotoxicity and cause aging and pathologies of various diseases and detoxification by the action of detoxification mechanisms (Rhee, SK, et al ,,, Lipid Content of Different Section and Fatty Acid Composition of Mackerel, Pacific Saury and sardine, pp. 82-88, 2001; Kim So Mi et al., Hyo Il, 2002; Oh, SH, Kim, DJ, .The Change in Content of Constitutive Lipid and Fatty Acid of Pacific Saury during Natural Freezing Dry (Kwa Mae Kee), Korean J. Food & Nutrition, pp.239-252, 1995).

Deep sea water is a deep sea water that is not more than 200m deep, and is a clean low temperature seawater resource rich in nutrients essential for the growth of marine plants and few organic matters or pathogens. (Korea ocean research Lab., 2000 ).

In addition to sodium chloride, seawater contains a large amount of magnesium, calcium, potassium, silicon, and the like, and it is also known to contain a small amount of trace elements, which are essential nutrients to the human body.

Seawater is called deep seawater, which is distinguished from surface water, and deep sea water refers to seawater 200 meters or less from the surface of seawater. It contains a lot of inorganic nutrients such as nitrogen, phosphorus, and silicic acid needed for plant growth because photosynthesis does not occur. In addition, since it is not polluted by air or chemicals, and is not polluted by solar or general bacteria, it has a small number of marine bacteria, so it has excellent physical cleanliness. It also contains a balance of essential trace elements and various minerals, and also has four minerals (magnesium and calcium). , Potassium, sodium), zinc, selenium, manganese, etc., and also excellent immune function against various diseases caused by stress or constitution, and is known to be very clean than surface water or ground water used as drinking water. In the current state of serious marine pollution, surface water is not suitable for food and beverage, but since deep sea water is not much more viable than surface layers and contains no pathogenic organisms, it is extremely safe to choose as a drink. (Japanese Patent Publication No. 7-34728).

The characteristics of deep ocean water are eutrophic (mineral) which is rich in nutrients decomposed by bacteria and contains a large amount of minerals such as calcium and magnesium because there is no phytoplankton consuming nutrients in the deep sea where sunlight does not reach. ), Less than 200 meters from surface seawater, low concentration of organic matter, no contamination by Escherichia coli or common bacteria, and less cleanliness, less likely to be polluted by chemicals from land or air. It has little change and stable low water temperature, and since deep sea water is water formed for thousands of years, its properties are stable, and it has matured ripened by the action of various enzymes. Balanced mineral content of dissolved metal ions It is known to have properties such as an excellent scavenging effect on active oxygen.

Such deep sea water is obtained by heating and concentrating seawater, cooling the concentrate, and then removing the crystals obtained from the concentrate, and continuing until the volume of the concentrate is concentrated to 1/1000 or less of the original volume. The enhancer and its manufacturing method are described, and a healthy drink effective for the prevention of modern diseases such as diabetes, allergic disease, myocardial infarction, etc. is disclosed by adding a part of the solution to the beverage (Japanese Patent Publication No. 2580428).

In addition, an electrolyte such as sodium chloride is added to the deep sea water and subjected to electrolysis in an electrolysis device. The strongly acidic oxidation water obtained from the positive electrode side (the redox potential is higher than 1000 mV at pH 2.4 to 2.7 or lower) and the alkali reduced water obtained from the negative electrode side are known. (See Japanese Patent Laid-Open No. 2001-198575).

In addition, focusing on the minerals contained in deep sea water, essential minerals such as metals and urea, such as copper and zinc, in addition to calcium and magnesium, which are known as minerals, have been identified. It has been known to develop vitamins as a nutritional beverage by adding vitamins to seawater that has reduced sodium chloride content (Japanese Patent Publication No. 60-255729), and since the number of viable bacteria is smaller than the surface water, this deep water is added to the beverage as natural mineral water. It has also been developed as a mineral beverage (Japanese Patent Laid-Open No. 5-219921).

In addition, beverages in which bitter juices and mines are obtained by taking seawater into fresh water dewatered using a reverse osmosis apparatus are known (Japanese Patent Laid-Open No. 10-150960). .

However, the above-mentioned manufacturing processes have a problem such that mineral concentrates and water containing or without minerals may be produced because they undergo an evaporative concentration step such as reverse osmosis or electrolysis. In addition, research has been conducted on mineral water beverages in which mineral components obtained from deep water obtained by desalting are added (Japanese Patent Laid-Open No. 2001-190256).

Such deep water is developed as a gel preparation for skin treatment such as atopic dermatitis (Japanese Patent Laid-Open Publication No. Hei 9-110702), or blended into food processed products such as tofu, and quasi-drug products (Japanese Patent Laid-Open Publication No. Hei 9-28269). Based on this deep seawater, it is a manufacturing process that is used as a health drink by adding raw material juice, sugar raw materials, secondary raw materials, and drinking water (Japanese Patent Publication No. 5-219921) or during the process of making bread. A manufacturing method using deep water as a water or liquid used in water has been studied (Japanese Patent Laid-Open No. 2000-333592).

However, the deep sea water used in the above-mentioned prior art uses deep water collected from Fujiyama Bay, etc., near Japan.

In addition, the domestic research using deep sea water is limited to the method of manufacturing food using deep sea water layer, the method of preparing food and drinking water added with deep sea water, and the research on the composition showing the pharmacological effect using the deep sea water. Was not.

The deep sea water also has four major minerals (magnesium, calcium, potassium, sodium), zinc, selenium, manganese, etc., and also has excellent immunity against various diseases caused by stress or constitution. It is known that this balance is included and has properties such as an excellent scavenging effect on active oxygen by the action of dissolved metal ions.

Therefore, the present inventors are developing R & D for developing and using Korea's deep ocean water resources efficiently. To understand the characteristics of the deep water resources and the stability thereof, not only for stable quality control but also for determination of intake water depth, etc. It is an important procedure. Based on the scientific evidence, we studied the composition of the prevention and treatment of deep obesity, hyperlipidemia and atherosclerotic vascular disease in deep sea water.As a result, we prepared a sample prepared with the addition of an obesity inducing ingredient (beef tallow). In the animal model that induced the deep seawater, the serum triglyceride and cholesterol levels were decreased.In the animal model in which hypercholesterolemia was induced by high cholesterol diet, hepatic and fecal lipid content was decreased and serum triglycerides were decreased. By reducing the cholesterol, phospholipids, lipid peroxide and Hydroxyl radical content, and enhancing the SOD activity in the serum, the present invention was confirmed to be useful for the prevention and treatment of obesity or hyperlipidemia and atherosclerotic vascular disease.

In order to accomplish the above object, the present invention provides a pharmaceutical composition for the prevention and treatment of obesity or hyperlipidemia and atherosclerotic vascular disease containing deep sea water as an active ingredient.

The present invention also provides a health functional food for the prevention and improvement of obesity or hyperlipidemia and atherosclerotic vascular disease containing deep sea water as an active ingredient.

The deep sea water, as defined herein, comprises its own or desalted concentrate and is located at about 300 to 1300 m, preferably about 500 to 1100 m, from the East Coast, West Coast or South Coast of the Republic of Korea, preferably from the East Sea surface. Ingested deep ocean water, most preferably Gangwon deep water (605m) or waterbis (1032m, Deep seawater), including sodium, calcium, magnesium, potassium, as well as selenium (Se), It has a feature of containing a large amount of inorganic ions having anticancer activity such as zinc and metal ions such as iron, manganese and stronium.

Deep sea water of the present invention can be used directly through the sterilization process or desalination treatment through a desalination process method well known in the art,

For example, specifically, the deep seawater collected is subjected to a desalination process using a cationic or anionic ion exchange resin, the deep water is evaporated through natural drying, or some water is removed after the natural drying. An electrolysis method is performed by evaporating to separate sodium chloride crystals from the concentrate obtained by concentrating the concentrated deep water by heating through a filter paper, or decomposing the sodium chloride component through a two-stage electrolysis device. The desalted concentrate may be subjected to a drying process such as natural drying, hot air drying, and lyophilization to prepare a desalted and dried deep water powder.

Alternatively, a desalting method using an ion exchange resin may be used. For example, a cation exchange resin or an anion exchange resin may be used for desalination fixing through an ion exchange resin, and a preferred cationic exchange resin is AG 50W-x8, Amberlite ( Strongly acidic cation exchange resins such as Amberlite) IR-120, Doexx 50W-x8 and the like; Weakly acidic cation exchange resins such as Amberlite IRC-50, Bio-Rex 70, Duoolite-436 and the like; Weakly basic cation exchange resins such as Amberlite IRA-67, Doex 3-x4A, and the like; Strongly basic cation exchange resins such as AG 2x8, Amberlite IRA-400, Doex 2-x8 series and the like; Or exchange resins composed of improved fibrous celluloses such as cation exchange resins such as CM-cellulose, SE-cellulose, and anion exchange resins such as DEAE cellulose; Or made of crosslinked dextran, eg, G-25 and G-50 beaded cation Sephadex-type resins, eg agarose, eg Sepharose CL and Biogel A Sepharose-type resins Or improved bead type ion exchange resins such as Fractogels or Toyopearl resins are preferred, and even more preferred exchange resins are those of the weakly basic anion exchange resin, Toyopearl DEAE type exchange resins. The exchange resin can be desalted using TOYOPELL DEAE-650C type exchange resin.

Alternatively, a desalination method using an electrolysis method may be used. For example, the electrolysis device used in the desalination method using an electrolysis method is not limited thereto, provided that it is used to electrolyze water, for example, a diaphragm. Using this divided tank, water is decomposed for a certain period of time by water supply to the reservoir, and water is continuously supplied through tap water. As the electrolytic apparatus, a cathode is a ferrite electrode, a platinum-plated titanium electrode, a titanium platinum sintered electrode, and the like. A cathode is a stainless steel electrode, a platinum-plated titanium electrode, a titanium platinum sintered electrode, or the like. The electrolysis device of is preferable.

Hyperlipidemia and atherosclerotic vascular diseases as defined herein are specifically hyperlipidemia, arteriosclerosis, heart failure, hypertensive heart disease, arrhythmia, congenital heart disease, myocardial infarction, angina pectoris, stroke or peripheral vascular disease, preferably hyperlipidemia or arteriosclerosis to be.

The pharmaceutical composition of the present invention comprises 0.1 to 50% by weight of the deep sea water based on the total weight of the composition.

However, the composition is not limited thereto, and may vary depending on the condition of the patient, the type of disease, and the progress of the disease.

The deep sea water itself of the present invention is a drug that can be used with confidence even when taken for a long time for the purpose of prevention because there is little toxicity and side effects.

The compositions of the present invention may further comprise suitable carriers, excipients and diluents conventionally used in the manufacture of pharmaceutical compositions.

The composition of the present invention may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterilized injection solutions, Examples of carriers, excipients and diluents that can be included in the composition containing the extract include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate , Cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and the solid preparations may include at least one excipient such as starch, calcium carbonate, sucrose in the extract. ) Or lactose, gelatin and the like are mixed. In addition to simple excipients, lubricants such as magnesium styrate talc are also used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included . Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

The preferred dosage of the composition of the present invention varies depending on the condition and the weight of the patient, the degree of disease, the type of drug, the route of administration and the period of time, but can be appropriately selected by those skilled in the art. However, for the desired effect, the deep sea water of the present invention is in the solution state of 0.5 L / kg to 5 L / kg per day, preferably 1 L / kg to 3 L / kg, powder form 0.5 g / day It is preferred to administer from kg to 5 g / kg, preferably from 1 g / kg to 3 g / kg. The administration may be carried out once a day or divided into several doses. Thus, the dosage amounts are not intended to limit the scope of the invention in any manner.

The composition of the present invention can be administered to mammals such as rats, mice, livestock, humans, etc. by various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine or intracerebroventricular injections.

The present invention also provides a health functional food for the prevention and improvement of obesity or hyperlipidemia and atherosclerotic vascular disease containing deep sea water as an active ingredient.

The composition containing the deep sea water of the present invention may be used in various applications, such as drugs, foods and beverages for the prevention and improvement of obesity or hyperlipidemia and atherosclerotic vascular disease. Foods to which the deep sea water of the present invention may be added include, for example, various foods, beverages, gums, teas, vitamin complexes, health supplements, and the like, and may be used in the form of powders, granules, tablets, capsules, or beverages. Can be.

Deep sea water of the present invention may be added to food or beverage for the purpose of preventing and improving obesity or hyperlipidemia and atherosclerotic vascular disease. At this time, the amount of the deep sea water in the food or beverage is generally added to the health food composition of the present invention 1 to 5% by volume of the total food weight, the health beverage composition is 0.02 to 10 ml, preferably based on 100 ml Preferably in a ratio of 0.3 to 1 ml.

In addition to containing the deep sea water as an essential ingredient in the indicated ratio, the health beverage composition of the present invention has no particular limitation on the liquid component and may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks. . Examples of the above-mentioned natural carbohydrates include monosaccharides such as disaccharides such as glucose and fructose such as maltose, sucrose and the like and polysaccharides such as dextrin, cyclodextrin and the like Sugar, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those described above, natural flavoring agents (tauumatin, stevia extract (e.g., Rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The proportion of said natural carbohydrates is generally about 1-20 g, preferably about 5-12 g per 100 mL of the composition of the present invention.

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 drinks, and the like. In addition, the compositions of the present invention may contain flesh for the production of natural fruit juices and vegetable beverages. These components can be used independently or in combination. The proportion of such additives is not so critical, but is generally selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.

Deep sea water of the present invention reduces the lipid content of liver tissue and feces in the hyperlipidemia-induced animal model, decreases the content of triglycerides, cholesterol, phospholipids, lipid peroxide and Hydroxyl radical in serum, and enhances SOD activity in serum It can be used in pharmaceutical compositions and health functional foods useful for the prevention and treatment of obesity or hyperlipidemia and atherosclerotic vascular disease.

Hereinafter, the present invention will be described in detail by reference examples, examples and experimental examples.

However, the following Reference Examples, Examples and Experimental Examples are merely illustrative of the present invention, and the content of the present invention is not limited to the following Reference Examples, Examples and Experimental Examples.

Example  1. Preparation for experiment

1-1. Preparation of Experimental Materials

Gangwon deep water (Gangwon deep water, 605m, Deep seawater, hereinafter referred to as "KW") and Waterbis (waterbis, 1032m, Deep seawater, referred to as "WB") are each purchased and sterilized and named in the following experiment Was used.

1-2. Deep ocean water Desalination Processing example  One

20 kg each of the deep water and the waterbis were added to the supply tanks of the positive and negative electrodes of the two-layer low-water electrolysis apparatus, and a direct current of 0.1 to 3.0 A was allowed to flow for 60 minutes, followed by desalination at the cathode side after the electrolysis was completed. 7 kg of the treated deep water desalting solution (hereinafter referred to as “KWD”) and 8 kg of waterbis desalting solution (hereinafter referred to as “WBD”) were obtained.

1-3. Deep ocean water Desalination Processing example  2

20 kg each of the deep water and the waterbis were added to the respective feed tanks of the positive and negative electrodes of the two-layer low-water electrolysis apparatus, and a direct current of 0.1 to 3.0 A was passed through a current for 60 minutes, and then the electrolysis was completed. The solution was collected and heated at 80 to 120 ° C. for 24 hours. The concentrated solution was left to stand at room temperature for 2 days and dried to obtain 150 mg of deep water desalted powder (hereinafter referred to as “KWDP”) and 200 mg of waterbis desalted powder (hereinafter referred to as “WBDP”). "Is obtained.

1-4. Mineral measurement

Minerals (Na, Ca, Mg, K, Fe, Co, Cd, P, Mn, B, Cu, Se, As, Zn, Ni, Cr, Si, Pb) take about 0.5-1 g of sample and add 12 mL of nitric acid. After the addition, dissolve and cool by microwave for 1 hour. 50 mL fill-up with tertiary distilled water was analyzed by ICP-OES (PerkinElmer precisely optical emission spectrometer, Optima 5300DV).

Reference Example  1. Preparation for experiment

1-1. Experimental Animal, Experimental  Configuration

Four weeks old males were obtained from SPF 25 ± 3 g ICR male mice and 140 ± 10 g Sprague Dawley (SD) rats (Hyochang Science Co., Ltd.). After healthy breeding, only healthy animals were used for the experiment. The breeding environment of this study was conducted in the laboratory animal breeding room (TECNIPLAST, Italy) of Kyungsung University pharmacy set at a temperature of 22 ± 3 ℃, a relative humidity of 50 ± 10% and an illumination time of 12 hours (07: 00 ~ 19: 00). Feed was freely ingested for drinking water, which was a solid feed for animals (Central Experimental Animal, Seoul). 24 hours before the experiment time only watering and fasting. At this time, the experimental animals were treated within a predetermined time (10: 00-12: 00 am) in consideration of the daily variation of enzyme activity.

1-2. Sample  Produce

Each deep water was administered using oral needle zonde to each experimental group for 4 weeks at 100, 200 mL / kg doses using 4% tween 80 diluted with saline.

1-3. Statistical analysis

The mean ± standard deviation of the three test results was shown. To test the homogeneity of variance, Duncan's multiple range test was used to determine statistical significance when the difference was less than 5% ( p <0.05). (Meaning that there is a statistically significant difference between the superscript alphabets in the data).

Experimental Example  1. Obesity and hyperlipidemia experiment

1-1. Induction of obesity and hyperlipidemia

Obesity and dietary hyperlipidemia in experimental animals were induced by raising beef tallow-prepared samples for 6 weeks (see Table 1).

1-2. Serum and Enzyme  pharmacy

Blood was collected from the abdominal aorta by light anesthesia with CO ₂ , and the collected blood was left for 30 minutes and centrifuged at 3,000 rpm for 10 minutes to separate serum and lipid peroxide (lipid peroxide). ), Hydroxy radical content and superoxide dismutase activity.

1-3. Body weight and fat tissue weight measurement

Body weight change was measured every week from the start of the experiment, the weight of the adipose tissue was calculated by taking the fat around the abdominal cavity and testicles.

1-4. Liver tissue  And Feces  Heavy lipid content measurement

Liver tissues were weighed and stored frozen at -70 ^o C, and feces collected for the last 4 days. Triglycerides and cholesterol were measured according to the method described in the literature (Folch et al., 1957).

In other words, the stool was lyophilized (PVTFD 300R-Korea Ilshin Lab) and pulverized, and the liver tissue was chopped and then ground with homogenase (teflon homogenizer; ULTRA TRURRAX T25 Dasic, MALAYSIA). 10 times the amount of solvent (chloroform: methanol = 2: 1) was added to the sample, and the lipids were repeatedly extracted. Methanol was added thereto to dissolve well, and then quantified using kit (Asan Pharmaceuticals) using the enzyme method.

1-5.Total Lipids Total lipid Content measurement

The absorbance at 540 nm was measured at 540 nm by heating the lipids together with the dark yellow phase and adding vanillin phosphate by the method of Fringe and Dunn (Fringe & Dunn, 1970) using the principle of the sulfo-phospho-vanillin reaction. . The blood content was expressed in mg / dl according to the standard calibration curve.

1-6. Total cholesterol ( Total cholesterol Content measurement

Experiments were carried out using a kit (AM 202-K, Asan) prepared by an enzyme method such as Richmond (Richmond W et al., 1976). Enzyme reagents (containing 20.5 U / l cholesterol, oxidase 10.7 U / l, and sodium hydroxide 1.81 g / l) were dissolved in enzyme reagent solution (potassium phosphate monobasic 13.6 g / l, phenol 1.88 g / l). 3.0 ml of the enzyme solution prepared in 20 μl of the sample was added to the dissolved solution, followed by incubation at 37 ° C. for 5 minutes, and the absorbance was measured at a wavelength of 500 nm using the reagent blank as a control. The blood content was expressed in mg / dl according to the standard calibration curve.

1-7. Triglyceride ( Triglyceride Content measurement

Experiments were performed using a kit (AM 157S-K, Asan) prepared according to the method of McGowan (McGrowan Mw et al., 1983). Enzyme reagents (containing lipoprotein lipase 10800U, glycerol kinase 5.4U, peroxidase 135000U, and L-α-glycero phosphooxidase 160U) in ice-cold phase were dissolved in enzyme reagent [N, N-bis (2-hydroxyethyl) -2-aminomethane sulfonic acid 0.427 g / dl containing 3.0 ml of the enzyme solution prepared in 20 µl of the sample was incubated at 37 ° C. for 10 minutes, and the absorbance was measured at a wavelength of 550 nm based on the reagent blank. The blood content was expressed in mg / dl according to the standard calibration curve.

1-8. Phospholipids ( Phospholipid Content measurement

Experiments were carried out using a kit (Iatron Chem. Co.) prepared by the enzyme method of Chen (Chen PS et al., 1956). In an ice-cooled solution, the enzyme reagent (containing phospholipase 3.9U, choline oxidase 5.6U, peroxidase 3.6U, and 4-aminoantipyrine 0.3252 mg) was dissolved in enzyme reagent solution [containing tris (hydroxymethyl) -aminomethane 6.057 mg]. 3.0 ml of the prepared enzyme solution was added, followed by incubation at 37 ° C. for 20 minutes to measure absorbance at a wavelength of 500 nm. The content was expressed in mg / dl according to the standard calibration curve.

1-9. High density lipoprotein - cholesterol ( HDL -C) content determination

The experiment was carried out using a kit (AM 203-K, Asan) prepared by the enzyme method of Noma (Noma A et al., 1986). 0.2 ml of sedimentation reagent (containing dextran sulfate 0.1% and magnesium chloride 0.1M) was added to 20 µl of serum, and the mixture was mixed well, left at room temperature for 10 minutes, and centrifuged at 3000 rpm for 10 minutes. 0.1 ml of the supernatant was mixed well with 3.0 ml of enzyme solution, incubated at 37 ° C. for 5 minutes, and the absorbance was measured at a wavelength of 500 nm using the reagent blank as a control. The content was expressed in mg / dl according to the standard calibration curve.

1-10. LDL - cholesterol  Content measurement

Low density lipoprotein-cholesterol (LDL-C) content was calculated by the following equation (1) according to the method of Fridewald.

1-11. Blood Lipid peroxide  Content measurement

According to the method described in the literature (Yagi K. 1987), 20 ml of serum was added and mixed with 4.0 ml of 1 / 12N H ₂ SO _4, 0.5 ml of 10% phosphotungstic acid was added thereto, and the mixture was left at room temperature for 5 minutes, followed by centrifugation to remove the serum as a precipitate. The protein was taken out and centrifuged again with 2.0 ml of 1 / 12N H ₂ SO ₄ and 0.3 ml of 10% phosphotungstic acid. 1.0 ml of a solution of 4.0 ml of distilled water, a mixture of 0.67% thiobarbituric acid and acetic acid in a 1: 1 manner was added thereto, and the mixture was reacted at 95 ° C. for 60 minutes, cooled at room temperature, and 5.0 ml of n-BuOH was added. After centrifugation for a minute, the resulting red n-BuOH was taken and absorbance was measured using a spectrofluorometer (Ex: 515 nm, Em: 553 nm). The absorbance was measured by reacting tetraethoxypropane 0.5 nmole with the standard solution in the same manner, and the serum lipid peroxide content was calculated by Equation 2 below.

1-12. Blood Hydroxyl radical  Content measurement

According to the method of Kobatake (Kobatake Y et al., 1987), in 34.8 μl of serum, 333.3 μl of 0.54 M NaCl, 0.1 M potassium phosphate buffer (pH 7.4), 10 mM NaN ₃ , 7 mM deoxyribose, 5 mM ferrous ammonium sulfate and distilled water The mixture was added so as to mix well in the vortex and allowed to stand at 37 ° C for 15 minutes. 67 μl of serum was taken and mixed with 75 μl of 8.1% sodium dodecyl sulfate, 500 μl of 20% acetic acid and 25 μl of distilled water. 333 μl of 1.2% thiobarbituric acid was added thereto, followed by heating in a water bath (100 ° C.) for 30 minutes, cooling at room temperature, and centrifugation at 700 × g for 5 minutes to measure absorbance at a wavelength of 532 nm. The content of hydroxyl radical (nmole / mg protein) was quantified by the calibration curve.

1-13. Blood Superoxide dismutase ( SOD Activity measurement

It was quantified according to the method of Oyanagui (Oyanagui, Y. 1984). The serum was diluted 100-fold with potassium phosphate buffer, and 100 μl of this was added to the test tube. Add 200 μl of 0.1 mM EDTA-2Na), mix well, and then stand in a 37 ° C. water bath for 40 minutes. 2.0 ml of Reagent C (300 mg of sulfanilic acid / 5.0 mg N-1-naphthyl-ethylenediamine in 500 ml of 16.7% acetic acid) was added to the reaction solution, which was allowed to stand at room temperature for 20 minutes, and then the absorbance was measured at 550 nm. The superoxide dismutase activity in serum was measured. Enzyme activity was expressed as U / mg protein of superoxide dismutase. One unit of SOD was calculated as 50% inhibition of adrenochrome production.

1-14. Protein Quantitation and Statistical Processing

Protein content was measured using bovine serum albumin (Sigma, Fr. V) as a standard according to the method of Lowry (Lowry OH, 1951). The results obtained in this experiment were expressed as mean ± standard deviation, and statistical significance was verified by Duncan's multiple range test.

2. Experimental results

2-1. Mineral measurement

The results of examining the depth water mineral content by depth are shown in Tables 2 to 3. The K content of 605m deep water and 1032m deep water was 694 and 372 mg / L, which was 1.9 times higher. Na and Ca contents were 11050, 10922, 356.3 and 366.7 mg / L, respectively, and Mg contents were 1323 and 1264 mg / L. The remaining mineral content was not detected (Table 2; see Table 3).

2-2. Weight change

Body weight was measured every week from the start of the experiment, the weight of the adipose tissue was measured after taking the abdominal cavity and peri testicular fat on the last day of the experiment is shown in Table 4 and Table 5. As a result, the 6 weeks of high cholesterol diet intake of hyperlipidemia induced the body weight of 6 weeks at 328.6 ± 21.6g compared to the normal diet (week 6, 213.9 ± 39.5g) 53% weight It was confirmed that the increase. In addition, as a result of administering the depth-by-depth water to the hyperlipidemic animals, the weight loss effect was significantly higher than that of the control group, and the weight loss effect was excellent in the depth-605m depth group. In addition, as shown in Table 5, as a result of administering the deep water to the hyperlipidemic animals, the weight loss effect was confirmed in both the abdominal cavity and the testicular adipose tissue in the deep water group compared to the control group. It was confirmed that the presence (Table 4; Table 5).

2-3. serum Phospholipid  content

As a result of the experiment, as shown in Table 6, the depth of the total lipid, phospholipid and neutral lipid in the serum was significantly decreased in the experimental group compared with the control group when the depth of water was administered to the experimental animals induced by hyperlipidemia by the high cholesterol diet. It could be confirmed that. In particular, the depth of 605m deep water treatment group was significantly reduced (see Table 6).

2-4. serum cholesterol  Content change and arteriosclerosis index

Depth by depth was administered to experimental animals induced by hyperlipidemia due to high cholesterol diet, and compared to the total cholesterol content (89.3 ± 4.25 mg / dL) in the serum of the control group. It was confirmed that the contents decreased to 84.6 ± 3.29 mg / 3.8 and 83.8 ± 3.16 mg / ㎗, respectively (see Table 7).

There was no significant difference in serum HDL and LDL cholesterol levels compared to the control group, but the atherosclerosis index (AI) (LDL-C / HDL-C) was compared with the control group (1.74 ± 0.12mg / dL). The 1032m and 605m depth water treatment groups significantly decreased to 1.55 ± 0.09mg / dL (12%) and 1.49 ± 0.15mg / dL (16%), respectively, indicating that they were effective in atherosclerosis.

2-5. Lipids in liver tissue and cholesterol  Content change

Table 8 shows the effects of oral administration of deep water on dietary hyperlipidemia in the change of lipid and cholesterol content in liver tissues. In rats fed dietary hyperlipidemia orally administered with deep water, the cholesterol content in hepatic tissue was lower in all experimental groups than in the control group. On the other hand, the depth of 605m deep water group significantly decreased. This can be seen that deep water administration affects the lipid metabolism of liver tissue, and indirectly proves that it is effective in diseases such as hyperlipidemia (see Table 8).

2-6. Serum peroxide lipids ( Lipid peroxide ) content

Lipid peroxide in serum of hyperlipidemia induced 6 weeks of high cholesterol diet was 51.9 ± 4.26nmole / ml, which was 1.8 times higher than normal diet (27.8 ± 3.25nmole / ml). It could be confirmed (see Table 9). In addition, it was confirmed that the hyperlipidemic animals decreased to 48.6 ± 4.11 nmole / ml and 47.2 ± 3.19 nmole / ml in the deep water 1032m and 605m deep water administration groups, respectively.

2-7. Blood hydroxyl radical  Generated and superoxide dismutase ( SOD ) activation

As a result, as shown in Table 10, the hydroxyl radical in the serum of hyperlipidemia induced hyperlipidemia after 6 weeks of high cholesterol diet was 5.63 ± 0.37 nmole / mg, normal diet (2.93 ± 0.28 nmole) / mg) compared to 1.9 times, and the hyperlipidemic animals were found to have a significantly lower effect of reducing the amount of Hydroxyl radicals in serum compared to the control group when 1032m deep water and 605m deep water were administered. In addition, it was confirmed that Superoxide dismutase (SOD) activity to remove the active oxygen was significantly enhanced in all the deep water administration group (see Table 10).

Hereinafter, the formulation examples of the composition containing the alkaline water of the present invention will be described, but the present invention is not intended to limit the present invention, but is only intended to be described in detail.

Formulation example  One. Powder  Produce

KWDP 20 mg

Lactose 100 mg

Talc 10 mg

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

Formulation example  2. Preparation of Tablets

WBDP 10 mg

Corn starch 100 mg

Lactose 100 mg

2 mg magnesium stearate

After mixing the above components, tablets are prepared by tableting according to a conventional method for preparing tablets.

Formulation example  3. Manufacture of capsule

KWDP 10 mg

3 mg of crystalline cellulose

Lactose 14.8 mg

Magnesium Stearate 0.2 mg

The above components are mixed according to a conventional capsule preparation method and filled in gelatin capsules to prepare capsules.

Formulation example  4. Preparation of injections

WB 10 mL

180 mg mannitol

Sterile sterilized water for injection 2974 mg

Na2HPO4,12H2O 26 mg

(2 ml) per 1 ampoule according to the usual injection preparation method.

Formulation example  5. Liquid  Produce

KW 20 mL

10 g of isomerized sugar

5 g of mannitol

Purified water

Each component was added to purified water in accordance with the usual liquid preparation method and dissolved, and the lemon flavor was added in an appropriate amount. Then, the above components were mixed, and purified water was added thereto. The whole was adjusted to 100 ml with purified water, And sterilized to prepare a liquid preparation.

Formulation example  6. Manufacture of health food

WB 1000 mL

Vitamin mixture quantity

70 [mu] g of vitamin A acetate

Vitamin E 1.0 mg

0.13 mg vitamin B1

0.15 mg of vitamin B2

0.5 mg vitamin B6

0.2 [mu] g vitamin B12

10 mg vitamin C

Biotin 10 μg

Nicotinic acid amide 1.7 mg

50 ㎍ of folic acid

Calcium pantothenate 0.5 mg

Mineral mixture quantity

1.75 mg of ferrous sulfate

0.82 mg of zinc oxide

Magnesium carbonate 25.3 mg

15 mg of potassium phosphate monobasic

Secondary calcium phosphate 55 mg

Potassium citrate 90 mg

100 mg of calcium carbonate

Magnesium chloride 24.8 mg

The composition ratio of the above-mentioned vitamin and mineral mixture is mixed with a composition suitable for a health food in a preferred embodiment, but the compounding ratio may be arbitrarily modified. The granules may be prepared and used for preparing a health food composition according to a conventional method.

Formulation example  7. Manufacture of health drinks

KW 1000 mL

Citric acid 1000 mg

100 g of oligosaccharide

Plum concentrate 2 g

Taurine 1 g

Purified water was added to a total of 900 ml

The above components were mixed according to a conventional health drink manufacturing method, and the mixture was heated at 85 DEG C for about 1 hour with stirring, and the solution thus prepared was filtered to obtain a sterilized 2-liter container, which was sealed and sterilized, &Lt; / RTI &gt;

Although the composition ratio is a mixture of the components suitable for the preferred beverage as a preferred embodiment, the blending ratio may be arbitrarily varied according to the regional and national preferences such as the demand level, the demanding country, and the intended use.

Claims (6)

A pharmaceutical composition for the prevention and treatment of obesity or hyperlipidemia and atherosclerotic vascular disease containing deep sea water as an active ingredient. The method of claim 1,
The deep sea water is a pharmaceutical composition of its own or desalted concentrate. The method of claim 2,
The deep sea water is a pharmaceutical composition that is deep sea water taken from the surface of the East Sea about 300 to 1300 m. The pharmaceutical composition of claim 1, wherein the hyperlipidemia and atherosclerotic vascular disease are hyperlipidemia, arteriosclerosis, heart failure, hypertensive heart disease, arrhythmia, congenital heart disease, myocardial infarction, angina pectoris, stroke or peripheral vascular disease. Health functional food for the prevention and improvement of obesity or hyperlipidemia and atherosclerotic vascular disease containing deep sea water as an active ingredient. A dietary supplement according to claim 5 which is a powder, granule, tablet, capsule or beverage.