WO2018062733A1 - Composition comprising green tea extract for improving blood glucose control, prepared using desalted lava seawater - Google Patents

Abstract

The present invention relates to a composition for improving blood glucose control, the composition comprising a green tea extract, which is prepared using desalted lava seawater and, more specifically, to a composition for improving blood glucose control, the composition comprising, as an active ingredient, a green tea extract, which is prepared using desalted Jeju lava seawater as an extraction solvent. The green tea extract prepared using desalted lava seawater according to the present invention can improve the blood glucose concentration and can be used in the manufacturing of a medicinal product, a functional food, and a cosmetic product, which can reduce the risk of occurrence of cardiovascular disease through the activation of bio-functions.

Description

Blood sugar control improvement composition comprising green tea extract prepared using desalted lava seawater

The present invention relates to a composition for improving blood sugar control comprising a green tea extract prepared using desalted lava seawater, and more particularly, comprising a green tea extract prepared using desalted Jeju lava seawater as an extractant as an active ingredient. It relates to a composition for improving blood sugar control.

Metabolic syndrome refers to a combination of diseases such as impaired glucose tolerance, hypertension, hyperlipidemia, obesity, and cardiovascular atherosclerosis due to chronic metabolic disorders that last for more than six months or one year. According to various epidemiologic data to date, about 25% of the population of developed and developing countries have metabolic syndrome, and the prevalence rate in Korea continues to increase. Metabolic syndrome is clinically closely related to two major diseases. One is various cardiovascular diseases caused by atherosclerosis, and metabolic syndrome increases the risk of coronary artery disease, cerebrovascular and peripheral vascular disease by 2-3 times. It is known to let. In addition, metabolic syndrome is a prognostic disease of type 2 diabetes, and as metabolic syndrome develops and leads to diabetes, the risk of associated cardiovascular disease is also amplified.

The cause of metabolic syndrome is not yet clear, but it appears to be caused by aging, changes in lifestyle and eating habits, and increased environmental pollution. Metabolic syndrome has four clinical symptoms. First, obesity causes more weight than the standard and the ratio of waist circumference to hip circumference increases. Secondly, due to insulin resistance, diabetes is not only defective in insulin itself, but also due to obesity or lack of exercise, insulin receptors are reduced and insulin secretion does not work. Thirdly, as the concentration of cholesterol and triglycerides in the blood increases, defects in lipid metabolism occur, and the concentration of lipids in the blood increases, resulting in cardiovascular diseases of hyperlipidemia and cardiovascular atherosclerosis. The last symptom is high blood pressure. Metabolic processes, such as the removal of lipids in blood vessels, cause defects in lipid accumulation and thereby increase blood pressure.

Metabolic syndrome, a chronic disease, is a disease that usually results from lifestyle, and it is known that it can be treated to some extent by changing this habit. In the gown, treatment through dietary habits is suggested as the most effective method. Atherosclerotic disease, in particular, is a major disease that increases mortality and morbidity among modern people. Atherosclerosis is a symptom due to the precipitation of lipids and calcium in the artery linings associated with inflammation. These symptoms include the accumulation of endothelial cells, lipids, and mononuclear cells that affect the vortices of blood such as hypercholesterolemia, hypertension, obesity, and diabetes. Will be affected. Damage to the lining of the intima can lead to platelet deposition and thrombosis, which can lead to fatal consequences such as stroke and myocardial infarction. Maintaining lifestyle changes (TLCs), including diet and exercise, is clearly helpful to prevent this, but most chronic illnesses are often difficult to correct only by lifestyles, which can lead to management of lipid-lowering medications. Is needed.

Fat cells are one of the major cells for glucose metabolism and play a very important role in blood sugar control. Glucose transport is carried out by glucose transporters (GLUTs), and in order to increase glucose transport, the expression of glucose transporters and the positional shift of the receptors to the cell membrane must be increased. Metastasis of the receptor to the cell membrane is known to be involved in signaling by insulin.

'Insulin' is a hormone that regulates the blood sugar, and when the concentration of glucose in the blood increases the insulin secretion in the pancreas increases glucose into the cells, thereby maintaining a constant concentration of glucose in the blood at all times.

In normal people, the body's insulin sensitivity (effect) and insulin secretion are balanced so that blood sugar is always regulated within the normal range. However, when insulin is deficient or susceptible to susceptibility, blood sugar cannot be used to increase the concentration of insulin in the blood. In addition, the body's susceptibility to insulin is reduced, increasing insulin resistance. The insulin resistance leads to a weak state of promoting the absorption of sugar, which is the main action of insulin in skeletal muscle, fat cells, and liver. Due to such insulin resistance, even if the amount of insulin in the body is about the same, the blood glucose lowering action is weakened, and accordingly, more insulin is required to maintain blood sugar normal. Accordingly, the phenomenon in which a large amount of insulin is secreted into the body to supplement insulin resistance is called hyperinsulinemia. In addition, excessive secretion of insulin increases appetite, promotes fat synthesis, and inhibits lipolysis, thereby inducing obesity. That is, the problem of insulin resistance is reported to be closely related to metabolic syndrome such as diabetes, hypertension, obesity.

'Diabetes' refers to a disorder in which the balance between insulin sensitivity and insulin secretion in the body is broken, that is, insulin deficiency or insulin sensitivity is lowered and glucose is released into the urine because blood sugar is not controlled due to inability to use sugar in the blood. .

Diabetes is largely divided into type 1 diabetes and type 2 diabetes.

Type 1 diabetes mellitus, 'insulin dependent diabetes mellitus', is caused by a decrease in insulin production and secretion due to damage to the pancreatic beta cells that secrete insulin. In order to treat type 1 diabetes, insulin is generally administered externally to lower blood sugar levels. Type 2 diabetes, or insulin-independent diabetes, refers to a condition in which blood sugar levels are higher than normal and occurs when the balance of insulin secretion and the secretion of insulin from the pancreas is broken in peripheral tissues such as muscle, fat and liver. do. Most diabetics have insulin resistance and hyperinsulinemia before progressing to type 2 diabetes. In other words, type 2 diabetes lowers the action of insulin, which lowers the initial blood sugar level, resulting in insulin resistance that does not effectively absorb sugar and utilize it as energy in peripheral tissues, resulting in increased insulin secretion to lower high blood sugar. Hyperinsulinemia is seen. Failure to overcome this will eventually lead to type 2 diabetes. In Korea, the number of patients with type 2 diabetes has increased in recent decades.

Currently, the prescription of insulin, insulin secretagogue or hypoglycemic agent is mainly used to treat diabetes and diabetic complications. However, this treatment is limited in that it is not a fundamental disease treatment. In accordance with these findings, a method of improving insulin resistance or increasing insulin sensitivity has recently been proposed for the treatment of metabolic syndrome-related diseases including diabetes and diabetic complications or metabolic syndrome itself. That is, attempts have been made to treat diabetes and diabetic complications by returning blood glucose and triglyceride levels to normal to eliminate the need for external insulin or to reduce the concentration of insulin.

Two characteristics of type 2 diabetes are insulin resistance and pancreatic beta cell insulin secretion. In addition to certain genetic factors, acquired factors, such as obesity or frequent exposure to hyperglycemia, facilitate and intensify the development of diabetes. Frequent hyperglycemic exposure thus increases insulin resistance and causes beta cell dysfunction and death due to overload of pancreatic beta cells that secrete insulin. This is called glucose toxicity (Borona, 2008). As a type of early-onset type 2 diabetes, mutations in the glucokinase gene are characterized by inhibiting hepatic glucose uptake, resulting in postprandial hyperglycemia (Jiang et al., 2008), leading to glucose toxicity. As shown in this example, efforts to reduce postprandial hyperglycemia are an important part of the prevention and treatment of diabetes. Amylase inhibitors or glucosidase inhibitors are commercially available to reduce hyperglycemia after eating, but they can cause side effects in the gastrointestinal tract, such as loss of appetite and indigestion, by preventing mutations to monosaccharides. .

Green tea is a perennial evergreen plant belonging to the tea tree family, and has been drinking since the Three Kingdoms period, and recently, its value has been recognized as the functionalities of the green tea ingredients are gradually revealed. Green tea contains a large amount of useful ingredients such as polyphenols, caffeine, amino acids, and vitamin C. It has been found to be excellent for hangover and nicotine detoxification, fatigue recovery, cardiac action, and skin care. Antioxidant action, anti-cholesterol action, hypoglycemic action, anti-tumor action, platelet aggregation inhibitory effect on polyphenols have been proved, and its functionality has attracted much attention.

The leaves of the tea plant, Camellia sinensis , contain up to 36% polyphenols on a dry weight basis, but their composition varies depending on climate, season, variety and growth conditions. Green tea catechins are a major group of green tea polyphenols.

Tea quality is greatly influenced by the harvesting season, maturity, varieties and the surrounding environment such as soil, weather, fertilization, and the tea's chemistry changes according to the external conditions. The taste of green tea is a combination of astringent, bitter, umami and subtle sweetness. The bitterness and bitterness are due to catechin and caffeine, the umami is mainly due to amino acids, and free catechin is known to give sweetness to the aftertaste.

Catechin, the main physiologically active substance of green tea, is a polyphenol containing about 100 mg in a cup of green tea, mainly epigallocatechin gallate (hereinafter referred to as "EGCG") and epicatechin gallate (epicatechin gallate). Gallate catechin (hereinafter referred to as "GC"), other epicatechin (hereinafter referred to as "EC") and epigallocatechin (hereinafter referred to as "ECC"), and epigallocatechin (hereinafter referred to as "EGC"). It is composed of various kinds of catechins, and these ingredients are food materials having various bioregulatory functions such as anti-caries, antibacterial, antioxidant, deodorant action, blood glucose level and blood cholesterol elevation suppression, anti-tumor, and lipid peroxide production inhibitory action. As a practical application, it is widely used in the field of processed foods. These catechins are known to have three to four times the antioxidant effect of vitamin C and vitamin E.

In addition, catechins are water-soluble, but tea leaves also contain fat-soluble components such as vitamin E and β-carotene. These components are used to remove free radicals and active oxygen-derived products that adversely affect immune response or cancer in vivo. It is known to be involved, and at the same time, it can be expected that synergistic effects can be expected when ingested with catechins, which simultaneously act as antioxidants.

Although good effects of green tea extract or epigallocatechin gallate (EGCG) have been reported in relation to type 2 diabetes, it has not been developed as a drug for the treatment of diabetes. It has been reported that there is no effect on improvement of glycated hemoglobin (HbA1C) concentration, insulin resistance and inflammatory factors (Fukino et al., 2005).

Interestingly, oral green tea extracts have been reported to prevent absorption of glucose (Kobayashi et al., 2000) and cholesterol (Raederstorff et al., 2003) in the gastrointestinal tract. This is caused by gallate catechin (GC) in catechins, which not only inhibit Na-glucose cotransporter (SGLT1), which is responsible for glucose uptake in gastrointestinal cells, but also forms fatty micelles. Inhibits and reduces digestion of fats.

The dose of gallate catechin (GC) required is low oral bioavailability, so that humans can take it without significant side effects (Van Amelsvoort et al., 2001). However, gallate catechins (GCs), which enter the gastrointestinal tract, are eventually absorbed into the blood and affect blood sugar in the body. Therefore, the effect of orally administered green tea extract on diabetes can be seen as a combination of effects in the gastrointestinal tract and in blood. In some reports, oral administration of green tea extracts has been shown to reduce blood sugar levels during glucose loading testing in rats and humans (Sabu et al., 2002; Tsuneki et al., 2004).

However, these results are likely to reflect only the effect of blocking the absorption of glucose in the gastrointestinal tract of the green tea was performed almost simultaneously with sugar and green tea. In addition, rats have a significantly lower oral absorption rate than humans, so it is difficult to see the effect of green tea in the circulation during the experiment. Therefore, in order to know the effect of the green tea extract on the blood glucose and diabetes at the same time to know the effect in the blood, but this report is not known to date.

Magma Seawater is a water that has been aged for a long time after seawater has been naturally filtered through basalt and sanisil layers. It is a seawater that exists in freshwater groundwater and saltwater, that is, in a saltwater mixing zone. Jeju Special Self-Governing Province is distributed from Jocheon-eup to Namwon-eup and Seongsan-eup.

The water quality of lava seawater has little change in physical properties, the water temperature does not change from 16 to 18 ° C, and the pH (hydrogen ion concentration) has an average range of 7.5. In addition, lava seawater contains not only essential minerals such as sodium, magnesium, calcium and potassium, but also general useful minerals (iron, manganese, zinc, molybdenum, etc.) than deep seawater and deep water than general seawater and deep water. . Characteristically, lava seawater contains a large amount of useful components, so the industrial utilization value is very high.

Lava seawater is a clean groundwater resource with no detectable coliforms, nitrates, phosphates, or phenols, and lava saltwater obtained from this lava seawater because no harmful components such as arsenic, mercury, cadmium, or lead are detected. We believe that there are no obstacles to industrialization.

On the other hand, according to the prior art, Patent Document 1 below discloses a method for producing green tea leaves that increase the content of catechins, polyphenols, flavonoids and the like of green tea leaves using deep sea water as a method of producing high-functional green tea leaves, Patent Document 2 discloses a green tea extract composition having a high content of minerals and minerals such as catechins and polyphenols using deep sea water, and antioxidant, whitening, anti-wrinkle of green tea extract composition prepared using deep sea water as an extraction solvent, Although it discloses an anti-inflammatory effect, it is prepared using Jeju desalted lava seawater, and containing the green tea extract as an active ingredient, there is no disclosure about the composition for improving blood sugar control.

Under these technical backgrounds, the present inventors have developed a composition for improving blood sugar control, including green tea extract prepared using desalted Jeju lava seawater as an extractant.

[Preceding technical literature]

[Patent Documents]

(Patent Document 1) Korean Registered Patent No. 10-1002589 (2010.12.14)

(Patent Document 2) Korean Patent Registration No. 10-0959520 (2010.05.17)

Accordingly, the present inventors have made diligent efforts to develop a plant-derived ingredient that effectively lowers blood sugar levels and improves body metabolism. As a result, green tea extract prepared using desalted Jeju lava seawater as an extraction solvent has improved blood sugar control or glucose metabolism. It was confirmed that the improved efficacy, the present invention was completed.

Accordingly, it is an object of the present invention to provide a composition for improving glycemic control excellent in hypoglycemic effect.

In order to achieve the above object, the present invention provides a composition for improving blood sugar control comprising a green tea extract prepared by using desalted lava seawater desalted lava seawater as an active ingredient.

The present invention also provides a pharmaceutical composition for improving blood sugar metabolism or improving obesity, containing the composition as an active ingredient.

The present invention also provides a health functional food composition for improving blood sugar metabolism or improving obesity containing the composition as an active ingredient.

The present invention also provides a cosmetic composition for improving blood sugar metabolism or improving obesity containing the composition as an active ingredient.

The present invention also provides a method for improving blood glucose metabolism or improving obesity, wherein the green tea extract prepared using desalted lava seawater desalted from lava seawater is used as a blood glucose metabolism improving agent or an obesity improving agent. to provide.

The present invention also provides the use of green tea extract prepared using desalted lava seawater desalted lava seawater as a blood sugar metabolism improving agent or obesity improving agent in the manufacture of a dietary supplement composition for improving blood glucose metabolism or improving obesity. do.

The present invention also provides the use of green tea extract prepared using desalted lava seawater desalted lava seawater as a blood sugar metabolism improving agent or obesity improving agent in the manufacture of cosmetic compositions or cosmetics for improving blood sugar metabolism or improving obesity. do.

Green tea extract prepared by using the desalted lava seawater according to the present invention can be used in the manufacture of medicines, functional foods and cosmetics that can improve the blood sugar level and reduce the risk of cardiovascular disease through the activation of biological functions.

1 shows a method for producing desalted lava seawater.

2 is a graph showing the composition of the green tea extract prepared using desalted lava seawater.

Figure 3 shows the change in glucose transport capacity of adipocytes after the green tea extract prepared using desalted lava seawater to the adipocytes.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In general, the nomenclature used herein is well known and commonly used in the art.

The present invention relates to a composition for improving blood sugar control, comprising a green tea extract prepared by using demineralized lava seawater prepared by mixing mineral water with demineralized water desalted from Jeju lava seawater.

In one production example of the present invention, 'demineralized lava seawater' is obtained by mixing demineralized water obtained by reverse osmosis filtration (RO) of the collected Jeju lava seawater with mineral water obtained by electrodialysis (ED) of the collected Jeju lava seawater. Prepared (see FIG. 1). As a result, as shown in Table 1, the desalted lava seawater was confirmed to have a specified mineral composition (see Production Example 1).

In one embodiment of the present invention, after preparing the green tea extract using the demineralized lava sea water was analyzed the composition of the green tea extract. As a result, as shown in Fig. 2 and Table 2, when the desalted lava seawater was used as the extraction solvent, the content of the specific glycosylated substance (Mw = 256kDa) included in the green tea extract was increased, and the content of catechin was partially reduced (for example, , Epigallocatechin gallate (EGCG) content reduction) (see Preparation Example 2 and Example 1).

In another embodiment of the present invention, after treating the green tea extract prepared using the desalted lava seawater to the adipocytes, glucose transport ability was measured. As a result, as shown in Figure 3, the adipocytes treated only with distilled water or demineralized lava seawater did not have a statistically significant change in glucose transport ability, whereas the green tea extract extracted with demineralized lava seawater was compared with the green tea extract extracted with distilled water. Glucose traffic increased significantly. In particular, when the green tea extract extracted with distilled water in adipocytes was treated at a high concentration (200 ppm), the glucose transport ability in adipocytes was higher when the green tea extract extracted with demineralized lava seawater was treated at a lower concentration (100 ppm). Therefore, it was confirmed that the use of green tea extract extracted with demineralized lava seawater had a synergistic effect on increasing glucose transport ability of adipocytes (see Example 2).

Accordingly, the present invention relates to a composition for improving blood sugar control, comprising, as an active ingredient, green tea extract prepared by using desalted lava seawater desalted lava seawater.

The lava sea water defined in the present invention is excavated from 100 to 200m underground, preferably 150m underground in the basement of Handong-ri, Gujwa-eup, Bukjeju-gun, Eastern Jeju, 30-150m underground, preferably 44.35m, 86.35m or 126.35m underground. Intake of lava saltwater. The lava seawater is sterilized using a sterile filter, and then obtained in a dried form (for example, lava saltwater) using a method such as heating evaporation, vacuum evaporation, sun drying or ventilation drying, and then distilled water. It may be dissolved in an aqueous solution to prepare a composition for use in preparing various formulations.

In the composition for improving blood sugar control according to the present invention, the lava seawater may be used as drinking water when only the desalting step is adopted, and when the dehydration step is adopted, the lava seawater may be used as a mineral composition powder mixed with salts. When the dehydration step is complete, it can be used as a pure (salt-free) mineral composition powder. In a preferred aspect, the desalted lava water of the present invention specifically comprises V, Se, Ge, Fe, Zn, Mn, Sr, B, Mo, Na, Mg, K, Ca and Si. All of these minerals are minerals that have been found to be useful to the human body.

Green tea extract prepared using desalted lava seawater desalted from lava seawater according to the present invention is 0.01 to 50% by weight, preferably 0.1 to 50% by weight, and more preferably 0.1 to 10% by weight, based on the total weight of the composition. It may be contained. If it is less than 0.01% by weight, the effect of improving blood sugar control is insignificant, and if it exceeds 50% by weight, the formulation stability becomes worse, which is not preferable.

In the present invention, the green tea extract is added to 70 ~ 100 ℃ desalted lava seawater to the green tea for 1 to 24 hours (preferably 2 to 3 hours) at 70 to 100 ℃ (preferably 85 to 95 ℃) After treatment, it can be characterized by obtaining by filtration and reduced pressure at 65 ~ 75 ℃.

Desalted lava seawater at 70-100 ° C. (preferably 85-95 ° C.) was added to green tea and treated for 1 to 24 hours (preferably 2 to 3 hours) while maintaining the temperature, followed by filtration and 65 to Obtained green tea extract at 75 ° C. (preferably 68-72 ° C.) under reduced pressure, optionally sterilized using a sterile filter, and dried using methods such as heat evaporation, vacuum evaporation, sun drying or ventilation drying. It can be obtained in the form (for example, green tea extract powder), and the dried green tea extract can be prepared as an aqueous green tea extract by dissolving it in an appropriate amount in an aqueous solution such as distilled water.

In the present invention, the green tea extract may be characterized in that it contains a polysaccharide (molecular weight) of 200 ~ 300kDa (preferably 240 ~ 260kDa).

In the present invention, the desalted lava seawater may be prepared by mixing demineralized water obtained by desalting the Jeju lava seawater by reverse osmosis and mineral water obtained by concentrating Jeju lava seawater by electrodialysis.

In the present invention, the desalted lava seawater may be prepared by mixing the demineralized water and the mineral water in a volume ratio of 19: 1.

The demineralized water (RO demineralized water) is a microfiltration (MF) and / or ultrafiltration (UF) using a micro-filter having a 5 μm pore size of the collected Jeju lava sea water, any method known in the art, for example For example, flash evaporation, seawater freezing, reverse osmosis, ion exchange resin, electrodialysis or desalination using a commercially available electrodialysis or demineralization, but is preferably prepared by reverse osmosis , more preferably 1x10 ^- it is prepared by using ⁶ μm reverse osmosis using a membrane filtration (RO) having a standard remove salts dissolved in water lava.

The mineral water (ED mineral water) is any method known in the art, such as flash evaporation method, seawater freezing method after fine filtration and / or ultrafiltration using a micro-filter having 5μm pore size , Reverse osmosis, ion exchange resin, electrodialysis, or by using a commercially available electrodialysis or demineralization, but can be prepared by concentration by electrodialysis is prepared by varying the electrical conductivity value of mineral water It is preferable because the mineral concentration can be adjusted.

"Prefiltration" or "Ultrafiltration" usable in the present invention means that the target solute is fractionated according to the size and structure of the solute, which is a component of the mixed solution, through the pores of the membrane under a certain pressure. It is a process. In one example, the solution may be purified by performing a polysulfone (PS) membrane for separation of 0.1 μm or 750 kDa molecular weight cutoff (MWCO) at 5 to 40 psig and 4 to 60 ° C.

In general, microfiltration is a process preceding ultrafiltration and is used to separate particles of 0.1 to 10 μm from solution and to separate polymers having a molecular weight of 1 × 10 ⁵ g / mol. Microfiltration is also used to remove sediment, protozoa, large bacteria and the like. Microfiltration available in the present invention can be easily used to remove polymers, cell debris. In general, the microfiltration process is carried out using a pressure pump or a vacuum pump at a pressure of 0.1 to 5 m / s, preferably 1 to 3 m / s, and a pressure of 50 to 600 kPa, preferably 100 to 400 kPa.

Ultrafiltration is used to separate particles from 0.01 to 0.1 μm from solution, which generally corresponds to polymers having a molecular weight of ¹ × ^{10 3} to ¹ × 10 ⁵ Da. Ultrafiltration is used to remove proteins, endotoxins, viruses, and silica.

In the present invention, the hardness of the desalted lava sea water may be characterized in that 200 to 300 mg / L.

The present invention relates to a pharmaceutical composition (pharmaceutical composition) for improving blood glucose metabolism or improving obesity, which contains the composition for improving blood sugar control as an active ingredient in another aspect.

The pharmaceutical composition may further contain pharmaceutical aids such as preservatives, stabilizers, hydrating or emulsifying accelerators, salts for regulating osmotic pressure and / or buffers, and other therapeutically useful substances, and various oral agents in accordance with conventional methods. Or in parenteral dosage forms. Parenteral dosage forms may be transdermal dosage forms, for example, but not limited to, lotion, ointment, gel, cream, patch or spray formulations.

Determination of the dosage of the active ingredient is within the level of those skilled in the art, and the daily dosage of the drug depends on various factors such as less progression, onset, age, health condition, complications, etc. of the subject to be administered. Generally, the composition may be administered by dividing 1 μg / kg to 200 mg / kg, preferably 50 μg / kg to 50 mg / kg, once or three times a day, and the dosage may be determined by any method. Nor does it limit the scope of the invention.

Pharmaceutical compositions containing green tea extracts of the present invention may be used as pharmaceutical preservatives such as preservatives, stabilizers, hydrating or emulsifying accelerators, salts and / or buffers for controlling osmotic pressure and other therapeutically useful substances (carriers, excipients, diluents, etc.) It may further contain and can be formulated in various oral or parenteral dosage forms according to conventional methods.

The term "carrier" is defined as a compound that facilitates the addition of a compound into a cell or tissue. For example, dimethyl sulfoxide (DMSO) is a commonly used carrier that facilitates the incorporation of many organic compounds into cells or tissues of an organism.

The term "excipient" is a substance that is added to make it easier to take medicine or to have a certain color and form when the amount of the main medicine is small in the process of preparation of tablets or pills, such as lactose or starch. do.

The term "diluent" is defined as a compound that not only stabilizes the biologically active form of the compound of interest, but also is diluted in water to dissolve the compound. Salts dissolved in buffer solutions are used as diluents in the art. A commonly used buffer solution is phosphate buffered saline, because it mimics the salt state of human solutions. Because buffer salts can control the pH of a solution at low concentrations, buffer diluents rarely modify the biological activity of a compound.

Compositions containing green tea extracts as used herein may be administered to a human patient, as such, or as a pharmaceutical composition in combination with other active ingredients or with a suitable carrier or excipient, such as in combination therapy.

Carriers, excipients and diluents that may be included in the pharmaceutical composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose , Methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.

The oral dosage forms include, for example, tablets, pills, hard and soft capsules, liquids, suspensions, emulsifiers, syrups, powders, powders, fine granules, granules, pellets, and the like, and these formulations include surfactants in addition to active ingredients. , Diluents such as lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and glycine, and glidants such as silica, talc, stearic acid and its magnesium or calcium salts and polyethylene glycols. . Tablets may also contain binders such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and polyvinylpyrrolidine, optionally starch, agar, alginic acid or its sodium salt Pharmaceutical additives such as disintegrants, absorbents, colorants, flavors, and sweeteners. The tablets can be prepared by conventional mixing, granulating or coating methods.

In addition, the parenteral administration agent may be, for example, formulations such as injections, drops, ointments, lotions, gels, creams, sprays, suspensions, emulsions, suppositories, patches, and the like. It is not.

The pharmaceutical composition according to an embodiment of the present invention may be administered orally, parenteral, rectal, topical, transdermal, intravenous, intramuscular, intraperitoneal, subcutaneous. Pharmaceutical compositions according to one embodiment of the invention may be administered topically to the scalp, for example.

In addition, the pharmaceutically acceptable dose, ie dosage, of the active ingredient depends on the age, sex, and weight of the subject to be treated, the specific disease or pathology to be treated, the severity of the disease or pathology, the route of administration and the judgment of the prescriber. Will be different. Dosage determination based on these factors is within the level of skill in the art. The dosage may preferably be 10 mg / day to 10 g / day, but the dosage does not limit the scope of the invention in any way.

Since the green tea extract of the present invention is a natural substance, it is not toxic at all and can be continuously used in large amounts as a medicine.

Pharmaceutical compositions suitable for use in the present invention include compositions in which the active ingredients comprising green tea extracts are contained in an amount effective to achieve their intended purpose. More specifically, a therapeutically effective amount means an amount of a compound effective to prolong the survival of the subject to be treated or to prevent, alleviate or alleviate the symptoms of a disease. Determination of a therapeutically effective amount is within the capabilities of those skilled in the art, in particular in terms of the detailed disclosure provided herein.

A therapeutically effective amount for the green tea extract used in the methods of the present invention and a composition (compounds) containing it as an active ingredient can be determined initially from cell culture assays. For example, dose can be calculated in an animal model to obtain a range of circulating concentrations that includes an IC ₅₀ (half maximal inhibitory concentration) or EC ₅₀ (half maximal effective concentration) determined in cell culture. Such information can be used to more accurately determine useful doses in humans.

Toxicity and therapeutic efficiency of the green tea extracts described herein, or compositions (compounds) containing them as active ingredients, are described, for example, LD ₅₀ (fatal to 50% of the population), ED ₅₀ (50% of the population). To determine the dose with therapeutic effect for, and IC ₅₀ (the dose with therapeutic inhibitory effect for 50% of the population), can be estimated by means of surface pharmaceutical procedures in cell culture or in laboratory animals. The dose ratio between toxic and therapeutic effects is the therapeutic index and it can be expressed as the ratio between LD ₅₀ and ED ₅₀ (or IC ₅₀ ). Compounds showing high therapeutic indices are preferred. The data obtained from these cell culture assays can be used to estimate the range of doses used in humans. The dosage or dosage of such compounds is preferably in the range of circulating concentrations including ED ₅₀ (or IC ₅₀ ) in the absence or little toxicity.

The present invention relates to a health functional food composition for improving blood sugar metabolism or improving obesity, which contains the composition for improving blood sugar control as an active ingredient in another aspect.

In the present invention, the "functional food" or "functional food" means a food that improves the functionality of the general food by adding the green tea extract of the present invention to the general food. Functionality can be roughly divided into physical properties and physiological functions. When the extract of the present invention is added to general foods, the physical properties and physiological functions of general foods will be improved, and the present invention provides a food product of such an improved function as a comprehensive 'functional food. (Health functional food) "or" functional food (health functional food) ".

The health functional food containing the green tea extract of the present invention may contain other ingredients and the like which can give a synergistic effect to the main effect within the range of not impairing the main effect of the present invention. For example, it may further include additives such as perfumes, pigments, fungicides, antioxidants, preservatives, moisturizers, thickeners, inorganic salts, emulsifiers and synthetic polymer materials to improve physical properties. In addition, supplementary ingredients such as water soluble vitamins, oil soluble vitamins, polymer peptides, polymer polysaccharides and seaweed extract may be further included. The components may be appropriately selected and blended by those skilled in the art according to the formulation or purpose of use, and the amount of the additives may be selected within a range that does not impair the object and effect of the present invention. In addition, the compositions of the present invention can be used in the form of additives for other foods.

The formulation of the dietary supplement containing the green tea extract of the present invention is not particularly limited, but may be formulated into various forms, for example, tablets, granules, drinks, beverages, solutions, emulsions, viscous mixtures, tablets, powders, and the like. Can be. In addition, the health functional food administration may be administered by a variety of methods, such as simple drinking, injection, spray or squeeze method.

In addition, the health functional food of the present invention, for example, various foods, candy, chocolate, beverages, gums, tea, vitamin complexes, health supplements and the like, and can be used in the form of powders, granules, tablets, capsules or beverages Can be.

The green tea extract of the present invention may be added to food or beverage for the purpose of improving blood sugar metabolism or improving obesity. At this time, the amount of the extract in the food or beverage is generally added to the functional food composition of the present invention 0.01 to 50% by weight, preferably 0.1 to 20% by weight of the total food weight, the health beverage composition is 100 mL It can be added at a ratio of 0.02 to 10 g, preferably 0.3 to 1 g as a reference.

The health beverage composition of the present invention has no special limitation except for containing the extract as an essential ingredient in the indicated ratio, 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, for example polysaccharides such as maltose and sucrose, and conventional sugars such as dextrin and cyclodextrin. 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 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 adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated drinks, and the like. The compositions of the present invention may also contain pulp for the production of natural fruit juices and fruit juice beverages 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 from the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.

The present invention relates to a cosmetic composition for improving blood sugar metabolism or improving obesity, which contains the blood sugar control improving composition as an active ingredient in another aspect.

The cosmetic composition is not particularly limited in formulation, and may be appropriately selected as desired. For example, softening cream (skin lotion and milk lotion), nourishing cream, essence, nourishing cream, massage cream, pack, gel, essence, eye cream, eye essence, cleansing cream, cleansing foam, cleansing water, pack, powder, It may be prepared in any one or more formulations selected from the group consisting of body lotion, body cream, body oil and body essence, but is not limited thereto.

In the present invention, the blood glucose metabolism improvement may be characterized in that the blood glucose drop.

Hereinafter, the present invention will be described in more detail with reference to Examples. These examples are only for illustrating the present invention, it will be apparent to those skilled in the art that the scope of the present invention is not to be construed as limited by these examples.

Preparation Example 1 Preparation of Desalted Lava Seawater

Lava sea water defined in the present invention is excavated from 100 to 200m underground, preferably 150m underground in the basement of Handong-ri, Gujwa-eup, Bukjeju-gun, Eastern Jeju, 30-150m underground, preferably 44.35m, 86.35m or 126.35m underground One lava seawater.

Since the lava seawater withdrawal is not suitable for drinking water or product manufacture because of the high salt content, the desalting process was performed. That is, precision filtration using a water intake by Jeju lava water micro-filter having a 5μm pore size (microfiltration, MF) and / or ultra filtration (ultrafiltration, UF) and, 1x10 ^- station by using a membrane having a ⁶ μm standard osmosis filtration (RO) to remove salts dissolved in lava seawater.

Jeju lava seawater taken in order to replenish the demineralized water (demineralized water) with demineralized salt to an appropriate content is mixed with mineral water obtained by electrodialysis (ED) to produce 'demineralized lava seawater', but the volume ratio of demineralized water and mineral water The desalted lava seawater was prepared such that n = 19: 1. The electrodialysis was performed by separating the monovalent cation, the monovalent anion, and the divalent anion by using a membrane to separate the anode.

As a result, as shown in Table 1, the desalted lava seawater was confirmed to have a specified mineral composition.

Table 1 shows the main composition contained in the desalted lava seawater.

Analysis item	Content (ppm)
V (vanadium)	0.010
Se (selenium)	0.010
Ge (germanium)	0.001
Fe	0.010
Zn (Zinc)	0.003
Mn (manganese)	0.001
Sr (strontium)	0.319
B (boron)	0.511
Mo (molybdenum)	0.001
Na (sodium)	28.796
Mg (magnesium)	62.079
K (potassium)	0.781
Ca (calcium)	15.329
Si (silicon)	0.482

As shown in Table 1, the demineralized lava seawater had a high Mg content and the water hardness was very high at about 244 mg / L. (For reference, the hardness of drinking water commercially available in Korea is about 20 to 80 mg / L. 300 mg / L or more).

Preparation Example 2 Preparation of Green Tea Extract Using Desalted Lava Seawater

4.5 L of demineralized lava seawater at 85-95 ° C. was added to 300 g of green tea, followed by treatment for 2 to 3 hours while maintaining the temperature, followed by filtration and 82.7 g of green tea extract at 65-75 ° C. under reduced pressure.

Analysis of the mineral composition of the green tea extract extracted using the demineralized lava seawater showed that it contains 4.5 mg / g of Mg, and it contained 15 times more Mg than the green tea extract extracted with Samdasoo (Korea). For reference, the allowable amount of Mg for adults is 300-450 mg / day).

Example 1: Composition Analysis of Green Tea Extract Using Desalted Lava Seawater

Table 2 shows the composition (wt%) of the green tea extract prepared using different extracting solvents. The extraction solvent is Jeju freshwater, desalted lava seawater (Production Example 1) or land freshwater.

	Jeju freshwater (content: wt%)	Desalted lava seawater (content: wt%)	Land freshwater (content: wt%)
Gallated catechin (GC)	1.54	2.35	1.7
Epigallocatechin (EGC)	5.26	4.28	6.95
Catechin (C)	0.33	0.5	0.84
Caffeine (CF)	0.74	0.65	1.19
Epigallocatechin gallate (EGCG)	3.28	1.73	4.89
Epicatechin (EC)	1.21	0.87	3.07
Gallocatechin gallate (GCG)	0.31	0.36	0.36
Epicatechin gallate (ECG)	0.52	0.3	1.6
Catechin gallate (CG)	0	0.2	0
Total (eight kinds)	12.45	10.59	19.40
Total (4 types)	10.26	7.18	16.50

As a result, as shown in FIG. 2, when the green tea extract was analyzed by gel permeation chromatography (GPC), when the desalted lava seawater was used as the extraction solvent, the content of a specific polysaccharide (Mw = 256 kDa) included in the green tea extract was increased. Increased, and a slight decrease in the content of catechins (eg, reduced epigallocatechin gallate (EGCG) content).

Example  2: glucose Transport capacity  Measure

First, the fat precursor cells were divided into black 96-well plates for fluorescence measurement, and the fat precursor cells were differentiated into adipocytes, and then cultured in a serum-free medium for 16 hours. At this time, distilled water (negative control group) or desalted lava seawater, which is an extraction solvent, or green tea extract prepared using the extracting solvent was incubated with a serum-free medium. Next, 100 nM of insulin was treated with the cells to transfer the glucose transporter in the cytoplasm to the cell membrane, followed by further incubation for 30 minutes, and then the medium was removed and washed with warm assay buffer.

In order to measure glucose transport ability in adipocytes, fluorescently labeled glucose (2-NBDG) at 100 μg / ml was treated with adipocytes and incubated for 10 min. Then, after removing the medium used in the culture, the fat cells are washed with a buffer, and the amount of glucose (2-NBDG) that enters the adipocytes is fluorescence (excitation / emission = 485 nm / 535 nm) using a multi plate reader. (Tecan, Infinite® 200 PRO series). Here, when the value of 2-NBDG fluorescence is high, it means that the amount of glucose (2-NBDG) that enters adipocytes is large.

As a result, as shown in Figure 3, the adipocytes treated only with distilled water or demineralized lava seawater did not have a statistically significant change in glucose transport ability, whereas the green tea extract extracted with demineralized lava seawater was compared with the green tea extract extracted with distilled water. Glucose traffic increased significantly. In particular, when the green tea extract extracted with distilled water in adipocytes was treated at a high concentration (200 ppm), the glucose transport ability in adipocytes was higher when the green tea extract extracted with demineralized lava seawater was treated at a lower concentration (100 ppm). Therefore, it was confirmed that the use of green tea extract extracted with demineralized lava seawater had a synergistic effect on increasing glucose transport ability of adipocytes.

In addition, as shown in Figure 2, when the desalted lava seawater was used as the extraction solvent, the specific glycosylated substance (Mw = 256 kDa) content contained in the green tea extract was increased, the content of catechin was partially reduced (e.g., epigallocatechin Gallate (EGCG)) (see Example 1), compared to the green tea extract extracted with distilled water, it was shown to have a high hypoglycemic effect.

In addition, the green tea extract prepared using the desalted lava seawater according to the present invention has a hypoglycemic effect, and thus may be prepared as a medicine, functional food, or cosmetics for improving blood glucose metabolism or improving obesity.

Formulation examples 1 to 8 comprising green tea extract prepared using desalted lava seawater desalted from Jeju lava seawater of the present invention as an active ingredient may be commercialized (medicine, food, cosmetics) into various formulations, It can be controlled at an appropriate content ratio, taking into account the functionality, cost and other conditions of the product.

Formulation example  1: preparation of ointment

The ointment containing the green tea extract manufactured using the desalted lava seawater of this invention was prepared by mixing the components of Table 3 containing an oil phase component and an aqueous phase component.

Ingredient	Example (% by weight)
Purified water	Remaining amount
Green Tea Extract Using Desalted Lava Seawater (Preparation Example 1)	10.0
Caprine / Capryltriglycide	10.0
Liquid paraffin	10.0
Solbitan Sesquioleate	6.0
Octyldodeceth-25	9.0
Cetylethylhexanoate	10.0
Squalane	1.0
Salicylic acid	1.0
glycerin	15.0
Sorbitol	10.0

Formulation example  2: Preparation of Soft Capsules

Green tea extract 80 mg, vitamin E 9 mg, vitamin C 9 mg, palm oil 2 mg, vegetable hardened oil 8 mg, lead beetle 4 mg and lecithin 9 mg were prepared using desalted lava seawater, and the soft capsule filling solution was mixed according to a conventional method. . 400 mg per capsule was filled to prepare a soft capsule. In addition, a soft capsule sheet was prepared at a ratio of 66 parts by weight of gelatin, 24 parts by weight of glycerine, and 10 parts by weight of sorbitol solution and filled with the filler to prepare a soft capsule containing 400 mg of the composition according to the present invention.

Formulation example  3: preparation of tablets

Tablets were prepared by tableting the composition 600 mg prepared by mixing 50 mg of green tea extract, 10 mg of vitamin C, 515 mg of crystalline cellulose, 12 mg of carboxymethylcellulose calcium, 8 mg of silicon dioxide, and 5 mg of magnesium stearate, prepared using desalted lava seawater. It was.

Formulation example  4: Manufacture of Drink

Green tea extract prepared using desalted lava seawater, vitamin E 9mg, vitamin C 9mg, glucose 10g, citric acid 0.6g, and 25g of liquid oligosaccharides were mixed, and 300ml of purified water was added to each bottle to 200ml. After filling the bottle sterilized for 4 to 5 seconds at 130 ℃ to prepare a beverage.

Formulation example  5: Preparation of Granules

80 mg of green tea extract, vitamin E 9 mg, vitamin C 9 mg, 250 mg of anhydrous glucose, and 550 mg of starch, which were prepared using desalted lava seawater, were mixed, molded into granules using a fluidized bed granulator, and then filled into sachets.

Formulation example  6: Nutritional Cosmetics Milk Croissant Manufacturing

The nutrient cosmetics containing the green tea extract prepared by using the desalted lava seawater of the present invention by mixing the components of Table 4 including the oil phase component and the water phase component.

Ingredient	Content (% by weight)
Purified water	Remaining amount
Green Tea Extract Using Desalted Lava Seawater (Preparation Example 1)	0.1
Beeswax	4.0
Polysorbate 60	1.5
Sorbitan sesquioleate	1.5
Liquid paraffin	0.5
Montana 202 (Manufacturer: Seppic)	5.0
glycerin	3.0
Butylene glycol	3.0
Propylene glycol	3.0
Carboxy Vinyl Polymer	0.1
Triethanolamine	0.2
Preservative, coloring, flavoring	Quantity

Formulation example  7: Preparation of Massage Cream

A massage cream containing a green tea extract prepared by using the desalted lava seawater of the present invention was mixed by mixing the components of Table 5 including an oil phase component and an aqueous phase component.

Ingredient	Content (% by weight)
Purified water	Remaining amount
Green Tea Extract Using Desalted Lava Seawater (Preparation Example 1)	0.1
Beeswax	10.0
Polysorbate 60	1.5
Sebum 60 Cured Castor Oil	2.0
Sorbitan sesquioleate	0.8
Liquid paraffin	40.0
Squalane	5.0
Montana 202 (Manufacturer: Seppic)	4.0
glycerin	5.0
Butylene glycol	3.0
Propylene glycol	3.0
Triethanolamine	0.2
Preservative, coloring, flavoring	Quantity

Formulation example  8: Manufacture of Pack

A pack containing the green tea extract prepared by using the desalted lava seawater of the present invention was prepared by mixing the components of Table 6 including an oil phase component and an aqueous phase component.

Ingredient	Content (% by weight)
Purified water	Remaining amount
Green Tea Extract Using Desalted Lava Seawater (Preparation Example 1)	0.1
Polyvinyl alcohol	13.0
Sodium Carboxymethyl Cellulose	0.2
glycerin	5.0
Allantoin	0.1
ethanol	6.0
Pingzi-12 nonylphenyl ether	0.3
Polysorbate 60	0.3
Preservative, coloring, flavoring	Quantity

The specific parts of the present invention have been described in detail above, and it is apparent to those skilled in the art that such specific descriptions are merely preferred embodiments, and thus the scope of the present invention is not limited thereto. something to do. Thus, the substantial scope of the present invention will be defined by the appended claims and their equivalents.

Claims (17)

1. A composition for improving blood sugar control, comprising green tea extract prepared using desalted lava seawater, which has been desalted lava seawater, as an active ingredient.
2. The composition of claim 1, wherein the lava seawater is taken from Jeju Island 100 to 200m underground.
3. The composition of claim 1, wherein the green tea extract is contained in an amount of 0.01 to 50% by weight based on the total weight of the composition.
4. The method of claim 1, wherein the green tea extract is obtained by adding desalted lava seawater at 70-100 ° C. to green tea, treating it at 70-100 ° C. for 1-24 hours, and then filtering and decompressing at 65-75 ° C. Composition.
5. The composition of claim 1, wherein the green tea extract comprises a polysaccharide having a molecular weight of 200 kDa to 300 kDa.
6. The composition of claim 1, wherein the desalted lava seawater is prepared by mixing demineralized water obtained by desalting the lava seawater by reverse osmosis and mineral water obtained by concentrating the lava seawater by electrodialysis.
7. The composition according to claim 6, wherein the mixing ratio (volume ratio) of the demineralized water and the mineral water is 19: 1.
8. The composition according to claim 1, wherein the desalted lava seawater has a hardness of 200 to 300 mg / L.
9. A pharmaceutical composition for improving blood glucose metabolism or improving obesity, comprising the composition of any one of claims 1 to 8 as an active ingredient.
10. 10. The pharmaceutical composition of claim 9, wherein the improvement in blood glucose metabolism is a drop in blood glucose.
11. Health functional food composition for improving blood sugar metabolism or obesity containing the composition of any one of claims 1 to 8.
12. The dietary supplement composition according to claim 11, wherein the blood glucose metabolism improvement is a decrease in blood glucose.
13. A cosmetic composition for improving blood sugar metabolism or improving obesity, comprising the composition of any one of claims 1 to 8 as an active ingredient.
14. The cosmetic composition according to claim 13, wherein the blood glucose metabolism improvement is a blood glucose drop.
15. Use of green tea extract prepared by desalted lava seawater desalted lava seawater as a blood glucose metabolism improving agent or obesity improving agent in the manufacture of a pharmaceutical composition or drug for improving blood glucose metabolism or improving obesity.
16. Use of green tea extract prepared using desalted lava seawater desalted in lava seawater as a blood sugar metabolism improving agent or obesity improving agent in the manufacture of a dietary supplement composition for improving blood glucose metabolism or improving obesity.
17. Use of green tea extract prepared using desalted lava seawater desalted in lava seawater as a blood sugar metabolism improving agent or obesity improving agent in the manufacture of a cosmetic composition or cosmetic for improving blood glucose metabolism or improving obesity.

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