KR100623210B1 - A composition for the treatment of metabolic syndrome comprising beta-glucan and folium mori extracts as effective ingredients - Google Patents

Abstract

The present invention relates to a pharmaceutical composition and health functional food for treating metabolic syndrome comprising β-glucan and baekbaek extract as an active ingredient. When used together with β-glucan and baekryeok extract synergistically, it can be useful for the treatment of complex symptoms of metabolic syndrome.

Metabolic syndrome, diabetes mellitus, hyperlipidemia, β-glucan, extract

Description

{A COMPOSITION FOR THE TREATMENT OF METABOLIC SYNDROME COMPRISING BETA-GLUCAN AND FOLIUM MORI EXTRACTS AS EFFECTIVE INGREDIENTS}

1 is a photograph showing the histomorphologic changes of the kidneys of the STZ animal model.

Figure 2 is a photograph showing the histological changes of the liver of the STZ animal model.

In each photo above, a, b: Sham; c, d: media control; e, f: CAPT administration group; g, h: sPOL administration group; i, j: sFME dose group; k, l: MPF 50 mg / kg; m, n: MPF 100 mg / kg; And o, p: MPF 100 mg / kg administration group. H & E staining, Scale bars = 100 micrometers.

Bouchard C. Genetics and the metabolic syndrome. Int J Obes Relat Metab Disord 1995; 19 (suppl 1): S52-9.

Chen, F.-J., Nakashima, N., Kimura, I., Kimura, M., 1989. Hypoglycemic

activity of mulberry leaves ( Folium Mori ) and Cortex Mori radicis in

streptozotocin-induced diabetic mice fasted and none fasted. Wakan

Iyakugaku Kaisshi 6, 374-75.

Czop JK. The role of beta-glucan receptors on blood and tissue leukocytes in phagocytosis and metabolic activation. Pathol Immunopathol Res 1986; 5: 286-96.

Darina Slamenovaa, D., Laaja, J., Krizkovab, L., Koganc, G., Sandulac, J., Bresgend, N., Eckl, P., Protective effects of fungal (1-3) -β-D- glucan derivatives against oxidative DNA lesions in V79 hamster lung cells. Cancer Lett. 2003: 198: 153-160.

Estrada A, Yun CH, Van Kessel A, Li B, Hauta S, Laarveld B. Immunomodulatory activities of oat beta-glucan in vitro and in vivo. Microbiol Immunol 1997; 41: 991-8.

Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) JAMA. 2001; 285: 2486-2497.

Laaksonen DE, et al., American Journal of Epidermiology 2002; 156: 1070-1077.

Liese AD, Mayer-Davis EJ, Haffner SM. Development of the multiple metabolic syndrome: an epidemiologic perspective. Epidemiol Rev 1998; 20: 157-72.

Nomura T. Phenolic compounds of the mulberry tree and related plants. In: Progress in the Chemistry of Organic Natural Products (Herz W, Grisebach H, Kirby GW, Tamm Ch, eds.), Vol. 53. Springe: Vienna, 1988; 87-201.

Pershadsingh HA. Dual Peroxisome Proliferator-Activated Receptor-alpha / gamma Agonists: In the Treatment of Type 2 Diabetes Mellitus and the Metabolic Syndrome. Treat Endocrinol. 2006; 5 (2): 89-99.

Raven GM, Role of insulin resistance in human disease Diabetes. 1988; 37: 1595-607.

Sathishsekar D, Subramanian S. Beneficial effects of Momordica charantia seeds in the treatment of STZ-induced diabetes in experimental rats. Biol Pharm Bull. 2005; 28: 978-83.

Seljelid, R. A Water-soluble aminated β-1,3-D-glucan derivative causes regression of solid tumors in mice. Biosci. Rep. 1986: 6: 845-851

Svegliati-Baroni G, Ridolfi F, Casini A, Bendia E, Gaggiotti G, Orlandoni P, Pontiroli A, Benedetti A, Folli F. Insulin and insulin-like growth factor-1 stimulate proliferation and type I collagen accumulation by human hepatic stellate cells ; differential effects on signal transduction pathways. 1999; Hepatology 29: 1743-1751.

Singab AN, El-Beshbishy HA, Yonekawa M, Nomura T, Fukai T. Hypoglycemic effect of Egyptian Morus alba root bark extract: effect on diabetes and lipid peroxidation of streptozotocin-induced diabetic rats. J Ethnopharmacol. 2005; 100: 333-8.

Williams, DL, Pretus, HA, McNamee, RB, Jones, EL, Ensley, HE, & Browder, IW Development of a water-soluble, sulfated (1-3) -β-D-glucan biological response modifier derived from Saccharomyces cerevisiae . Carbohydr. Res. 1992: 235: 247-257.

Wolff SP. Diabetes mellitus and free radicals. Free radicals, transition metals and oxidative stress in the aetiology of diabetes mellitus and complications. Br Med Bull. 1993; 49: 642-52.

Zhanga, M., Peter C.K. Cheunga, L. Zhang, C. M. Chiua, V.E.C. Ooi. Carboxymethylated β-glucans from mushroom sclerotium of Pleurotus tuber-regium as novel water-soluble anti-tumor agent. Carbohydr. Poly. 2004: 57: 319-325.

The present invention relates to a composition for treating metabolic syndrome using a herbal medicine. Specifically, the present invention relates to a pharmaceutical composition and a dietary supplement for treating metabolic syndrome comprising β-glucan and an extract of baekbaek as an active ingredient.

Metabolic syndrome refers to a condition in which several diseases, such as diabetes mellitus, hypertension, hyperlipidemia, obesity, coronary or atherosclerosis, which occur due to chronic metabolic disorders, occur simultaneously, for the first time in 1988 by Reaven (Raven GM, 1988). Since it has been identified and started to be called X syndrome, it is a complex disease also referred to as insulin resistance syndrome.

According to the guidelines outlined in the 3rd Cholesterol Cholesterol Management Guidelines (NCEP-ATP III) of the International Cholesterol Education Program, metabolic syndrome is diagnosed as a combination of three or more combinations of diabetes or glucose tolerance, obesity, hypertension, and hyperlipidemia. JAMA 2001).

In the development of metabolic syndrome, acquired genetic factors as well as acquired environmental factors such as physical activity have been shown to play an important role, but the specific cause of the disease has not been identified, but it is closely related to insulin resistance. (Liese AD, 1998; Bouchard C. 1995). A common common symptom of this metabolic syndrome is impaired glucose tolerance, which is closely related to obesity, which may be accompanied by hypertension and hyperlipidemia (Laaksonen DE, et al. 2002).

Diabetes mellitus, a key symptom of metabolic syndrome, is represented by diabetes. Diabetes is a disease caused by abnormal carbohydrates. It is a chronic metabolic disease in which glucose is not used as an energy source in the body and thus remains high in blood and excreted in urine.

Diabetes can be roughly divided into insulin-dependent type 1 diabetes and non-dependent type 2 diabetes. Type 1 diabetics rarely secrete insulin due to genetic causes or viral infections, and type 2 diabetics are normal in the amount of insulin secreted. If blood glucose is not normalized due to abnormal insulin resistance and glucose utilization rate, the entire metabolic process of insulin is affected, and the representative ones are hyperlipidemia and hypertension due to abnormal lipid metabolism.

The metabolic syndrome is a global disease. According to recent epidemiological studies in the United States, about 65% of Americans with a large overweight population have metabolic syndrome.In Korea, 19% of men over 30 years of age, Sixteen percent of women were found to have metabolic syndrome (Huh Dong, Korean Journal of Internal Medicine, 63: 1-7, 2002).

However, metabolic syndrome is a recognized disease only recently, and the exact statistics are not yet available in Korea. Considering that a large number of diabetic patients are potential metabolic syndrome patients, the number will far exceed the above figure. I think.

Specifically, diabetes is a pan-human disease, and its number is increasing every year. (Sathishsekar and Subramanian, 2005). According to a 2003 International Diabetes Federation (IDF) survey, the world's number of diabetics is estimated at 194 million, and the actual number of patients is over 300 million, even when diabetes is not diagnosed. It is estimated that by 2025, the number of diabetics around the world will increase at least about 2-3 times as of today.

In Korea, according to a recent survey by the Korean Diabetes Association and the Korea Health Insurance Review and Assessment Service, as of 2003, the number of diabetics was 4.29 million, 8.29% of the total population, and 4.9 million in 2010. It is estimated that the number of patients, diabetes in 2020, and 7.2 million in 2030, one in every seven people, diabetes is a metabolic syndrome.

The most serious problem of metabolic syndrome is the occurrence of chronic complications such as diabetic retinopathy, nephropathy, neuropathy, hyperlipidemia and cardiovascular diseases (stroke, angina pectoris, myocardial infarction, peripheral vascular disease). For example, in diabetic patients, the risk of vision loss is 25 times higher, the risk of renal failure and limb amputation due to necrosis is 20 times higher than that of normal people, and the risk of coronary heart disease and ischemic brain disease is increased 2 to 6 times, respectively. (Wolff, 1993).

Most of these chronic complications, once they occur, are irreversible and, as yet, there is no way to completely block this process, which, if not properly treated, can lead to serious symptoms leading to death. do.

Therefore, in order to effectively manage or treat metabolic syndrome with multiple symptoms, it is ideal to simultaneously treat nephropathy, hepatopathy and hyperlipidemia with the hypoglycemic effect to maintain normal blood sugar, but such treatments have not been developed until now. , Blood sugar lowering agents, blood pressure lowering agents, cholesterol treatments, etc. are taken separately.

In the case of diabetes treatment, many diabetic drugs based on synthetic and herbal ingredients have been developed or under development, which are largely divided into oral hypoglycemic agents and insulin injections. In general, type 1 diabetic patients who do not secrete insulin are injected with insulin, and type 2 diabetic patients who are insulin independent are taking hypoglycemic agents. For patients with type 1 diabetes, much effort has been made in the development of therapeutic drugs for type 2 diabetes because there is substantially no other treatment alternative than insulin administration.

Oral hypoglycemic agents, which are used as the main treatments for patients with type 2 diabetes, can be classified into sulfonylureas and biguanide-based drugs, and a number of drugs and foods for improving, preventing and treating diabetes, including herbal medicines, have been developed. .

Korean Patent Publication No. 195886 discloses a composition for treating diabetes comprising 17 herbal ingredients, such as Cordyceps sinensis and cow sulfur.

Korean Patent Publication No. 126431 discloses a health food composition having a hypoglycemic effect including herbal ingredients such as cereals, green tea, and sulphur.

Korean Patent No. 395619 discloses a composition for treating diabetes comprising 15 herbal ingredients such as ginseng and rhubarb.

Korean Patent Laid-Open No. 237974 discloses a confectionery composition for diabetic patients containing baekbaekpi as a main ingredient.

Korean Laid-Open Patent Publication No. 1998-72435 discloses a confectionary composition whose main ingredient is cedar skin.

In addition, the leaf extract (Korean Patent Publication No. 1998-21670), Hong Kyung-cheon Extract (Korean Patent Publication No. 1997-32879), Green Tea Extract (A study on the blood glucose lowering component of Japanese tea, 108, 10: 964-970 , 1988), Jangsaeng Doraji Extract (Korean Patent Publication No. 2000-7447) and the like have been reported to have a hypoglycemic effect.

However, the therapeutic agent is focused on hypoglycemic, and none of the documents discloses a therapeutic agent having an effect simultaneously with hypoglycemia, hypertension and hyperlipidemia.

In addition, most of them are accompanied by side effects such as hypoglycemia, allergy, hyperlipidemia, polyuria, incomplete treatment effects such as hypoglycemia and prevention of complications, or most antidiabetic drugs including hypoglycemic agents containing conventional herbal ingredients It is made by combining various herbal preparations without the accurate pharmacological efficacy verification and clinical data, depending on traditional folk methods.

In addition, when only the mulberry medicine is used as a diabetes treatment agent, patients with high blood pressure usually have systolic blood pressure increase, and those with low blood pressure usually have diastolic blood pressure decrease and helplessness, and vomiting due to gastrointestinal disorders. Side effects of nausea, heartburn, headache and collapse have been reported.

The present invention has been completed in recognition of the above problems, has not yet been developed a drug of a natural raw material having a complex effect such as glucose tolerance, which can be effectively used for metabolic syndrome, resulting in hepatic and nephropathy, hypertension, or hyperlipidemia.

The present invention is a metabolic syndrome therapeutic agent and health functional food comprising β-glucan and baekbaek extract as an active ingredient that can be effectively used in the treatment of complex symptoms of metabolic syndrome, hypoglycemia, nephropathy, liver disease, choles and / or hyperlipidemia The purpose is to provide.

To achieve the above object, the present invention provides a pharmaceutical composition for treating metabolic syndrome comprising β-glucan or a derivative thereof, and an extract of baekbaek as an active ingredient.

The present invention also the β-glucan comprises a glucose main chain connected by β-1,3 bond, wherein at least one of the glucose is β-1,3 / 1, connected by branched glucose and β-1,6 bond, 6-glucan is provided.

The present invention also provides a composition wherein the β-glucan is derived from Aureobasidium pullulans SM2001.

The invention is also characterized in that the weight ratio of β-glucan to leach extract in the composition is about 1: 4.

The present invention also provides a dietary supplement for improving the symptoms of metabolic syndrome comprising β-glucan or a derivative thereof as an active ingredient.

Hereinafter, the present invention will be described in detail.

The present invention, as mentioned in the background, while searching for natural substances safe for the human body, which are effective in the treatment of metabolic syndrome with complex symptoms, such as hypoglycemia, nephropathy, hepatopathy, and / or hyperlipidemia, When combined with a water-soluble β-glucan having a topographic structure and the extract from the extract, it was found that there is a synergistic effect in the symptomatic treatment of metabolic syndrome to complete the present invention.

In this regard, the present invention provides a pharmaceutical composition for treating metabolic syndrome comprising β-glucan or a derivative thereof, and an extract of baekbaek as an active ingredient.

As used herein, the term “metabolic syndrome” is generally insulin resistant, as mentioned in the background, and is associated with impaired glucose tolerance or diabetes mellitus, hypertension, hyperlipidemia, obesity, coronary or mild vein sclerosis, when metabolic disorders take a chronic course. It means that several of the same diseases occur at the same time (Pershadsingh HA., 2006).

In this regard, the compositions of the present invention that are effective in treating metabolic syndrome can be effectively used for the treatment of symptoms including one or more of glucose intolerance, complications caused by glucose tolerance, hypertension, and hyperlipidemia. Complications due to the glucose tolerance or diabetes include nephropathy, hyperlipidemia or hepatopathy.

Beta-glucan is a natural substance widely used in industrial fields in various fields such as cosmetics, immune activators and anticancer agents in developed countries, and its stability in human use has been proven.

Glucan is a complex polysaccharide in the form of fibrin to which glucose is linked and classified into alpha-glucan and β-glucan. The former is generally present in starch of plants, the latter is known to be present in the cell walls of cereals, mushrooms and yeasts, and β-glucan is widely used in various industrial fields such as anticancer agents.

Grain-derived β-glucans such as yeast, mushrooms, barley and oats show differences in properties within β-glucans, depending on the linkage structure and physical properties of glucose. For example, β-glucan derived from mushrooms isolated from the fruiting body of shiitake mushroom is known to be water-soluble, activate the complement system that exhibits immune function such as infectious defense in vivo, dramatically improve immune function, and exert antitumor effect. [Czop, 1986; Estrada et al., 1997].

However, in the various plant-derived glucans including the glucans, no complex effects on hypoglycemia, hyperlipidemia and nephropathy, including lowering cholesterol levels in combination with other natural substances or alone, have not been disclosed.

Glucans are complex polysaccharides found in the cell walls of yeast, oats or barley, and mushrooms used for medical purposes, such as, for example, Maitake mushrooms, as mentioned in the background, and are derived from various plants and fungi that exhibit the effects of the present invention. β-glucan may be included in the composition of the present invention.

In particular, the β-glucan comprises a glucose main chain connected by β-1,3 bonds, and at least one of the glucose is water-soluble β-1,3 / 1, having a structure connected by branched glucose and β-1,6 bonds, 6-glucan or derivatives thereof.

Specifically, β-1,3 / 1,6-glucan is β-1,3 and β-1 in which one molecule of glucose is β-1,6 bound per 5 molecules of glucose connected by β-1,3 bonds. Branched β-glucan with 6 bonds mixed together. In addition to the β-1,3 bond, the physiological activity is higher than that of other linear β-glucans due to the β-1,6 bond.

The β-1,3 / 1,6-glucan has an amorphous structure with low crystallinity and has molecular weight ranging from hundreds of thousands to millions. It is also a water-soluble acidic polysaccharide that is readily dissolved in water because the lactic acid group is substituted for glucose branched in the main chain.

Water-soluble β-glucans also show improved results in various physiological activities than insoluble (Darina Slamenovaa, D. et al, 2003; Seljelid, R. A, 1986; Svegliati-Baroni G et al., 1999; Williams, DL et al, 1992; Zhanga, M. et al, 2004). The term derivative used in the present invention is a term known in the art, and the hydroxyl group of branched glucose is substituted with, for example, a carboxymethyl group, a sulfuric acid group, an amine group, and a sulfoethyl group and so on to be water-soluble β-glucan. It is to include.

In particular, β-1,3 / 1,6-glucan having the above characteristics has the structure of Formula 1 below.

[Formula 1]

(In Formula 1, n is 1 to about 4,000 and X is a lactic acid group, and other examples thereof include maleic acid or sulfoacetic acid.)

More specifically, the glucan is Aureobasidium Aureobasidium of the applicant's Korean Patent Registration No. 0443209 pullulans ) is a variant of Aureobasidium pullulans SM-2001 (KCCM 10307), and can be prepared according to the methods of preparing β-glucans known in the art or described in the patent specification.

Meanwhile, Morus species (Moraceae) is an old medicine used by mankind over 4000 years ago (Singab et al., 2005), and has been used as an anti-inflammatory, diuretic, expectorant and diabetic medicine in Chinese medicine (Nomura 1988; Chen). et al., 1995).

In particular, the mulberry root bark (leaf, upper leaf), eggplant (upper limb), etc. are used in connection with the treatment of diabetes, but as mentioned above, when used alone, systolic blood pressure rise in patients with high blood pressure In general, people with low blood pressure often have diastolic blood pressure and helplessness, and side effects such as vomiting, nausea, heartburn, and headache due to gastrointestinal disorders have been reported.

When used in combination with beta glucan, the baekbaek extract used in the present invention exhibited a hypoglycemic effect, a therapeutic effect on nephropathy, hepatopathy and hyperlipidemia, and these therapeutic effects were obtained by using β-glucan or baekbaek extract alone, respectively. It is significantly higher than that.

In particular, there was no therapeutic effect on diabetic complications when the extracts of Morus alba were used alone, but the combination with glucan was recognized as a very good therapeutic effect, and the therapeutic effect on diabetic complications in these combinations was superior to that of glucan alone. In particular, in the combination group containing 1: 4 glucan and baekryeok extract, the effect of remarkable hypoglycemic and diabetic complications was recognized than the same dose of baekryeek extract alone. Therefore, the effect of the combination of glucan and baekbaek extract on diabetes and diabetic complications is higher than when using glucan and baekbaek extract alone, indicating a marked synergistic effect by the combination of glucan and baekbaek extract. In addition, the results are consistent with the results of histological analysis of liver and kidney of rats with metabolic syndrome symptoms to which the composition of the present invention was administered (Examples 3, 4 and FIGS. 1 and 2).

Mulberry used in combination with glucan in the pharmaceutical composition of the present invention is a plant derived from Morus of Moraceae, for example, M. alba Linne , M. bombycis KOIDZUMI ), road-tree ( M. lhou KOIDZUMI ) or other homogenous plants can be used in the present invention. Extracts of the epidermis, upper or upper limb of each of these plants or mixtures of two or more of these extracts can be used in the present invention.

 The white extract or powder thereof used in the present invention may be prepared according to a known method using hot water extraction or a suitable organic solvent such as methanol, ethanol or the like as an extraction solvent (Nomura T, 1988). For example, each of the lettuce, upper limbs or upper leaves, or mixed in various combinations, put into a heated circulation extraction tank, and extracted with purified water or edible alcohol for about 6 hours at 80 to 100 ℃ and filtered to obtain a filtrate, the residue Repeat this process with purified water or edible alcohol. The filtrates can be combined and used as such or concentrated under reduced pressure with a vacuum concentrator, and the dried product obtained by hot air or lyophilization can be used by grinding with a grinder.

According to one embodiment of the present invention, β-1,3 / 1,6-glucan derived from aureobasidium pullulan SM-2001 to streptozotocin (STZ) -derived rats, a representative diabetic animal model As a result of administering the extract and the extract, it was confirmed that the therapeutic effect was significantly increased for the treatment of weight loss inhibition, nephropathy, hepatopathy, and hyperlipidemia, compared with the β-glucan alone. This proves the superiority of the composition of the present invention that, when used as a complex composition of β-glucan and baekbaek extract, can simultaneously exhibit an elevated therapeutic effect against hypoglycemia and diabetic complications.

The weight ratio of β-glucan to Morus extract (FM) in the compositions of the present invention ranges from about 1:10 to about 10: 1, in particular 1: 8, more particularly 1: 4.

The beta-glucan and leprosy extract of the present invention may be administered simultaneously or sequentially, either alone or in combination with other pharmaceutically active ingredients for the treatment of diabetes mellitus, diabetic complications such as liver disease or nephropathy, hyperlipidemia, cholesterol Can be administered.

Pharmaceutical compositions comprising β-glucan or derivatives thereof and extracts of the present invention are suitable carriers, diluents, preservatives, stabilizers, wetting agents, emulsifiers, solubilizers, sweeteners, colorants, osmotic pressure regulators commonly used in the manufacture of pharmaceutical compositions, Excipients such as antioxidants may be further included. Specifically, lactose, dextrose, sucrose, sorbitol, mannitol xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrroly Dough, water, methylhydroxy benzoate, propyl hydroxy benzoate, talc, magnesium, stearate, mineral oil, etc. are mentioned.

The method of administering the pharmaceutical composition for treating metabolic syndrome comprising β-glucan or a derivative thereof and an extract of baekbaek can be easily selected according to the formulation, powder, tablets, pills, granules, dragees, hard or soft capsules. Formulations may be in the form of solutions, solutions, emulsions, suspensions, syrups, elixirs, external preparations, suppositories, sterile injectable solutions and the like, which may be administered orally or parenterally or topically, with oral administration being preferred.

Solid dosage forms for oral administration include tablets, pills, powders, granules, capsules, and the like, which solid dosage forms include β-glucan or derivatives thereof and extracts of at least one excipient such as starch, calcium carbonate, shoe It is prepared by mixing cross or lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium styrate talc are also used. Liquid dosage forms for oral administration include suspensions, solutions, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. have.

Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and the suspension solvent, 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, glycerol, gelatin and the like can be used.

 Furthermore, pharmaceutical compositions comprising β-glucans or derivatives thereof and extracts of the present invention may be prepared using any suitable method known in the art or by Remington's Pharmaceutical Sciences (Recentington), Mack Publishing Company, Easton PA. Formulated preferably using the method disclosed herein.

The dosage of β-glucan or derivatives and extracts of the present invention may vary depending on the weight, age, sex, health condition, diet, time of administration, administration method, excretion rate and severity of the disease of the patient, The effective dosage of β-glucan or its derivatives and extracts of the extract in the pharmaceutical composition is typically 0.1 to 1000 mg / kg per day, especially 200 mg / kg per day for adults (70 kg), and can be administered one to several times a day . Since the dosage may vary depending on various conditions, it will be apparent to those skilled in the art that the dosage may be added or subtracted, and thus the dosage does not limit the scope of the present invention in any aspect.

The frequency of administration can be administered once a day or divided into several times within the desired range, the administration period is not particularly limited. In addition, the composition of the present invention may be ingested daily by adding to any food, in addition to oral administration as it is.

Pharmaceutical compositions comprising β-glucan or derivatives thereof and extracts of the present invention can be administered by various routes to mammals such as mice, mice, livestock, humans, and the like.

The pharmaceutical composition comprising β-glucan or derivatives and extracts of the present invention may not only provide excellent anti-diabetic effect, but also have no toxicity and side effects due to drugs, and thus can be used safely for long-term use.

Accordingly, the β-glucan or derivatives and extracts thereof may be used as the main, secondary and food additives of food.

 Accordingly, the present invention provides a health functional food for improving the symptoms of metabolic syndrome, including the β-glucan or a derivative thereof and a white extract described above.

According to one embodiment of the present invention, the beta glucan in the food includes a glucose main chain connected by β-1,3 bonds, and at least one of the glucose is a branched glucose and genothiobios connected by β-1,6 bonds. (gentiobiose), water-soluble β-1,3 / 1,6-glucan or derivatives thereof.

As used herein, the term "health functional food" is a food manufactured and processed using raw materials or ingredients having functional properties useful for the human body, and is useful for health uses such as nutrient control or physiological action on the structure and function of the human body. Ingestion means to achieve the effect.

Symptom improvement of metabolic syndrome means that the symptoms resulting from various diseases accompanying metabolic syndrome, for example, hyperlipidemia, hypercholesterolemia, hyperglycemia symptoms have been improved compared to before ingestion. The data can be used to know the exact criteria for hyperlipidemia, hypercholesterolemia, and hyperglycemia, and to determine the extent of improvement. According to one embodiment of the present invention the symptoms are improved by at least about 10% upon ingestion of the health food according to the present invention.

Health functional foods including the β-glucan or derivatives thereof and extracts of baekbaek may include drugs, foods and beverages in the form of tablets, capsules, powders, granules, liquids, and pills. Specifically, various foods, candy, chocolate, a drink, a gum, tea, a health supplement food, etc. are mentioned, for example.

At this time, the amount of the β-glucan or derivatives and extracts of the extract in the food or beverage is generally about 0.01 to about 50% by weight, preferably about 0.1 to about 20% by weight of the total food weight, health drink The composition may be included in a ratio of about 0.02 to about 10 g, preferably about 0.3 to about 1 g, based on 100 ml.

The dietary supplement may further include a food supplement acceptable food supplement additive together with β-glucan or a derivative thereof and a white extract.

The health beverage composition comprising the β-glucan or a derivative thereof and a white extract is not particularly limited in liquid components except for containing the β-glucan or a derivative thereof and a white extract as essential ingredients in the indicated ratios. Likewise, various flavors or natural carbohydrates can be contained as additional ingredients. Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose and fructose; Disaccharides such as maltose and sucrose; Conventional sugars such as polysaccharides such as dextrin, cyclodextrin and the like; And sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (tauumatin, stevia extract (for example, baudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can also be used. The ratio of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to about 12 g per 100 ml of the health beverage composition.

In addition, various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavoring agents, such as colorants and fillers (cheese, chocolate, etc.), pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective properties And colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated drinks, and the like. In addition, the nutraceuticals may contain flesh for the production of natural fruit juices and fruit juice drinks and vegetable drinks. These components can be used independently or in combination. The ratio of such additives is not critical but is usually selected in the range of about 0.01 to about 20 parts by weight per 100 parts by weight of the health functional food.

Hereinafter, examples are provided to help understand the present invention. However, the following examples are provided only to more easily understand the present invention, and the present invention is not limited to the following examples.

Example  1 β- used in the present invention Glucan  And White  Preparation of Extract

Example  1-1 β- Glucan  Produce

Β-glucan derived from Aureobasidium pullulans SM-2001 was prepared in powder as described in Korean Patent No. 0443209.

In summary, Aureobasidium pullulans SM-2001 (KCCM 10307) was inoculated into a culture medium containing glucose as a carbon source, followed by shaking culture at 30 ° C for 3 days. The culture solution was centrifuged to recover the supernatant, extracted with 95% ethanol and dialyzed, and then vacuum lyophilized to prepare a water-soluble β-1,3 / 1.6 glucan. The prepared glucan was stored at 4 ° C. to prevent light from being used until use.

Β-glucan from Aureobasidium pullulan SM-2001 is also commercially available (Glucan Corp., Korea).

Example  1-2 White  Preparation of Extract

Pour 4000 liters of water into 1 kg of baekbaek, heat it at 180 ° C for 18 hours, decoction, and filter the suction filtered filtrate with a rotary vacuum evaporator (NN type; LAB Camp, Dajeon, Korea) Extract was obtained and then lyophilized using a lyophilizer (PVTFD10A; ilShin Lab., Seoul, Korea) to obtain 550 g, (yield 55.00%) of water extract lyophilisate, and then, when administered, dissolved in an appropriate amount in sterile distilled water. Used.

The β-glucan and baekbaek extract were stored at 4 ℃ blocked from light until use.

Example  2 Preparation of animal model and administration of test substance

Example  2-1 Preparation of animal model of diabetes

In order to investigate the effects of β-glucan and leprosy extract on the metabolic syndrome, rats were treated with streptozotocin to prepare an animal model with complex symptoms of glucose tolerance, nephropathy, hepatopathy and hyperlipidemia as follows. .

During the experiment, feed and water were freely ingested during the day, and the temperature was kept at 20-25 ° C. and 40-45% humidity. In addition, the light-dark cycle in the cage was adjusted to repeat day and night every 12 hours.

Three hundred female rats (6 weeks old, 120-140 g, SLC, Japan) were added per cage to the surrounding environment for 7 days before being used in this experiment. 290 of these animals were intraperitoneally administered streptozotocin (STZ) dissolved in 50 mM citric acid buffer at a total concentration of 60 mg / kg / 5 ml. The remaining 10 animals were administered the same volume of medium (water) in the same way instead of STZ for use as Sham (normal group).

Example  2-2 Administration of Test Substance

β- Glucan  And White  Administration of the mixture of extracts

Β-Glucan (G) and Leave Extract (FM) prepared according to Example 1 were diluted in the amounts and combinations described in Table 1. The compositions of Table 1 were then orally administered to rats prepared according to Example 2-1 (23 days after STZ administration) once a day for 4 weeks using a 3 ml syringe with rat oral sonde. .

Administration of various symptomatic treatments of known metabolic syndrome as a control

As a positive control for the test of the metabolic syndrome treatment effect of the complex composition of the present invention comprising β-glucan and baekbaek extract, the effect on diabetic nephropathy was Captopril (CAPT) (trade name Capoten, Sigma, USA) (100 mg / kg / 5ml) and 100mg / kg group, the effect on diabetic hepatic and hyperlipidemia was Silymarin (SILY) 25mg / kg group, Milk Thistle, Sigma, USA, and the hypoglycemic effect was Glibenclamide (GLIB) (Donil, Sigma, USA) compared with the 5 mg / kg administration group.

Statistical analysis

After administration of the composite composition of the present invention, the weight of each rat, blood glucose, BUN, creatinine, AST and ALT concentrations, and total cholesterol, triglycerides, HDL and LDL concentrations were measured to determine general toxicity, hypoglycemia, and diabetes mellitus, respectively. The effects on nephropathy, hepatopathy and hyperlipidemia were measured in comparison with the normal group and the control group for the above-mentioned symptoms.

All data are expressed as mean ± standard deviation. The number of individuals per administration group, Sham, and Control is 6, and the statistical analysis is Mann-Whitney U-Wilcoxon Rank Sum W test (MW test) for SPSS for Windows (Release 6.1.3., SPSS). Inc., USA). For each of these variables, the percentage change relative to the media control was [(data of test-data of media control)] / data of media control] x 100; And percentage change for normal group was calculated from [(test group data-normal group data)] / normal group data] × 100.

Example  3 β- Glucan  And White  Effects of Extracts on Metabolic Syndrome

Changes in weight, blood sugar, BUN and creatinine, AST (Aspartate Transferase, GOT) and ALT (Alanine Transferase, GPT) after administration of the composition of the present invention to the STZ rats prepared according to Example 2 in the combination of Table 1 Was measured.

Example  3-1 Effect on Weight Change

Body weights were measured on the day of STZ administration (immediately before administration), on the day of administration of the compositions of the present invention, and at 7, 14, 21, 27 and 28 (rat sacrifice time), respectively. Before weighing, each animal was fasted overnight to reduce dietary errors.

The results are shown in Tables 2 and 3 below, and the abbreviations are as defined in Table 1.

Abbreviations are as defined in Table 1. In the table, p <0.01 compared to the normal group by the * MW test; #, ##: p <0.01 and p <0.05, respectively, as compared to the medium control group by the MW test.

In Table 3, 1) Change I: change in body weight during the diabetes induction period (change from the day of STZ administration to 23 days after STZ administration; 2) Change II: sacrifice from the day of administration of the composition of the present invention Weight change by time; *, **: p <0.01 and p <0.05, respectively, compared to the Sham control by MW test; #, ##: p <0.01 and p <0.05, respectively, as compared to the medium control group by the MW test.

As shown in Tables 2 and 3, a significant (p <0.01) weight loss began to be observed in all STZ-administered groups compared to the normal group from the start of administration. In addition, weight gain during the induction period also showed a significant decrease (p <0.01) compared to the normal group. This suggests that STZ administration effectively induced metabolic syndrome including glucose tolerance.

The weight gain during the administration period was -88.84% in the medium control group compared to the normal group, and -115.38 in the CAPT, SILY, GLIB, sPOL, sFME, MPF 50, 100 and 200 mg / kg administration groups, respectively. 350.00, -57.69, 273.08, 26.92, 365.38, 438.46 and 669.23%. All MPF-administered groups showed significant (p <0.01 or p <0.05) dose-dependent increase in body weight compared to media control, with weight gain rates of 365.38, 438.46 and 669.23% at MPF 50, 100 and 200 mg / kg, respectively. It is significantly higher than CAPT, SILY, GLIB, and is significantly higher than β-glucan alone or baek extract alone, demonstrating the synergistic effect of the combination of β-glucan and baek baek extract.

Furthermore, this synergistic effect on weight gain indicates that the composition comprising a combination of β-glucan and lettuce extract indirectly exhibits a therapeutic effect on metabolic syndrome and is not toxic even when taken for a long time.

Example 3-2 hypoglycemic effect

The concentration of glucose (glucose) in the blood is a direct and representative index indicating the effect of diabetes treatment. For blood glucose measurements, blood was drawn from the orbital plexus and vena cava, respectively, on day 6 of administration of STZ (day 0 of administration) and on day 28 after administration of the composition of the present invention, and a NaF-treated sugar vacuum tube (Becton Dickinson) , USA), and plasma was isolated. Blood glucose levels were measured using an automated blood analyzer (Toshiba 200FR, Japan) as recommended by the user. The results are summarized in Table 4.

Abbreviations are as defined in Table 1. In Table 4, 1) Change (I): changes in blood glucose during the administration period of the composition of the present invention (from day 0 to sacrifice); *: P <0.01, respectively, compared to the S normal group by the MW test; #, ##: p <0.01 and p <0.05, respectively, as compared to the medium control group by the MW test.

As shown in Table 4, in the medium control group, a significant (p <0.01) increase in blood glucose was recognized as compared to the normal group, and when the combination of β-glucan and the white extract was included, at the end of the administration, MPF 50, 100 And dose-dependent blood glucose reductions of -7.49, -9.88 and -14.58%, respectively, compared to the media control at and 200 mg / kg.

Furthermore, in the blood glucose change during the administration period, the media control group showed 1721.43% compared to the normal group, whereas the GLIB, sPOL, sFME, MPF 50, 100 and 200 mg / kg administration groups, respectively, -120.39,- Changes of 11.37, -79.61, -66.27, -105.10 and -128.63% (data not shown).

This is superior to Glibenclamide (GLIB) (-12.49% reduction), which is widely used as a drug for lowering blood sugar. Furthermore, the composition of the present invention comprising a combination of β-glucan and baekrye extract exhibits better blood glucose suppression effect at each single composition administration group (-2.09, -9.28% change in glucan and baekrye extract, respectively) at the same dose. It is believed that the synergistic effect on blood sugar drop is caused by β-glucan and extract from the extract.

Example 3-3 Diabetic Nephropathy  Treatment effect

Blood Urea Nitrogen (BUN) and creatinine concentrations are representative indicators of the incidence and extent of kidney disease. For determination of the concentrations of BUN and creatine, blood was collected from the orbital vein and the large vein, respectively, on day 21 of administration of STZ (day 0 of administration) and on day 28 after administration of the composition of the present invention, and plasma was isolated according to a known method. BUN and creatinine were measured using an automated blood analyzer (Toshiba 200FR, Japan) as recommended by the user. The results are summarized in Tables 5 and 6.

Blood BUN  Effect on concentration

Abbreviations are as defined in Table 1. In Table 4, 1) Change (I): BUN concentration change during the administration period of the composition of the present invention (from day 0 to sacrifice); *: P <0.01 compared with normal group by MW test; #, ##: p <0.01 and p <0.05, respectively, as compared to the medium control group by the MW test.

As shown in Table 5, the media control group showed a significant (p <0.01) increase in blood BUN content compared to the normal group, but it was significant (p < 0.01 or p <0.05) A decrease in blood BUN content was observed after the end of the administration. At the time of final necropsy, blood BUN content was 259.73% in the medium control group compared to the normal group, and -22.39, -28.25, 1.72 in the CAPT, sPOL, sFME, MPF 50, 100 and 200 mg / kg administration groups, respectively. , -16.89, -25.99 and -34.08%.

Furthermore, a significant (p <0.01 or p <0.05) decrease in blood BUN content during the administration period was also observed in all the administration groups except for the lateral mononuclear group. The change in blood BUN content during the administration period was 1275.61% in the medium control group compared to the normal group, and in the CAPT, sPOL, sFME, MPF 50, 100 and 200 mg / kg administration groups, respectively, -70.17,- 107.85, 5.12, -53.22, -84.30, and -131.82%.

The composition-administered group of the present invention comprising β-glucan and extract from the extract showed a dose-dependent decrease in blood BUN content and amount of change. On the other hand, the lateral single-body administration group showed a change in blood BUN content very similar to the medium control group.

Furthermore, the composite composition of the present invention showed a superior inhibitory effect on blood BUN content increase than that of each single composition-administered group at the same dose, which demonstrates the synergistic effect of the composite composition according to the present invention. It is also an excellent blood creatinine inhibitory effect comparable to the same dose of captopril (CAPT) widely used as a therapeutic agent for nephropathy.

Effect on blood creatinine concentration

Abbreviations are as defined in Table 1. In Table 5, 1) Change (I): BUN concentration change during the administration period of the composition of the present invention (from day 0 to sacrifice); *, **: p <0.01 and p <0.05, respectively, compared to the normal group by MW test; #, ##: p <0.01 and p <0.05, respectively, as compared to the medium control group by the MW test.

As shown in Table 6, the media control group showed a significant (p <0.01) increase in blood creatinine content compared to the normal group, but was significantly (p <0.01) higher than the media control group in all the administration groups except the lateral unilateral single composition group. <0.01 or p <0.05) Decrease in the blood creatinine content was confirmed after the end of the administration, and the blood creatinine content at the final necropsy was 62.35% in the medium control group compared to the normal group. CAPT, sPOL, sFME, MPF 50, Changes of -14.49, -17.24, 4.27, -12.25, -16.04 and -23.26% in the 100 and 200 mg / kg administration groups were compared with the media control, respectively.

Furthermore, a significant (p <0.01 or p <0.05) decrease in blood creatinine content during the administration period was also observed in all dose groups except for the lateral unilateral single composition dose group. The change in serum creatinine content during the administration period was 2386.67% in the medium control group compared to the normal group, and in the CAPT, sPOL, sFME, MPF 50, 100 and 200 mg / kg administration groups, -57.10,- 66.49, 15.95, -51.07, -63.14 and -94.64%.

In the composition administration group of the present invention comprising β-glucan and baekryeok extract showed a dose-dependent decrease in blood creatinine content and amount of change. On the other hand, the lateral single-body administration group showed a change in blood creatinine content very similar to the medium control group.

Furthermore, the composite composition of the present invention showed a superior inhibitory effect on the increase in creatinine content in the blood than the administration of each single composition at the same dose, which demonstrates the synergistic effect of the composite composition according to the present invention. It is also a good blood creatinine inhibitory effect comparable to the same dose of captopril (CAPT) widely used as a therapeutic agent for nephropathy.

Example 3-4 Caregiving  Treatment effect

Aspartate Transferase (AST) and Alanine Transferase (ALT) are representative indicators of the presence and extent of hepatopathy, expressed in units of International Units per liter (IU / L). Blood was collected from the orbital vein and the abdominal vein, respectively, on day 6 (AST) and day 21 (ALT) of STZ administration and on day 28 after administration of the composition of the present invention, and plasma was isolated according to a known method. AST and ALT concentrations in isolated plasma were measured using an automated blood analyzer (Toshiba 200FR, Japan) as recommended by the user. The results are summarized in Tables 7 and 8, respectively.

Blood AST  Effect on concentration

Abbreviations are as defined in Table 1. In the above table, 1) Change I: Change in AST concentration over the period of administration of the composition of the present invention (from day 0 to sacrifice); *: P <0.01 and; compared to Sham control by MW test; #, ##: p <0.01 and p <0.05, respectively, compared to the medium control group by MW test.

As shown in Table 7, the media control group showed a significant (p <0.01) increase in blood AST (GOT) content compared to the normal group, but was significantly higher than the media control group in all the administration groups except the lateral mononuclear group. Decrease in (p <0.01 or p <0.05) blood AST content was recognized after the end of dosing. At the final autopsy, the blood AST content was 626.63% in the medium control group compared to the normal group, and -26.72, -28.78, 0.22 in the SILY, sPOL, sFME, MPF 50, 100, and 200 mg / kg groups, respectively. , -19.48, -27.32 and -37.57%.

Furthermore, a significant (p <0.01 or p <0.05) decrease in blood AST content over the administration period was also observed in all dose groups except for the lateral unilateral single composition dose group. The change in blood AST content during the administration period was 4733.90% in the medium control group compared to the normal group, and in the SILY, sPOL, sFME, MPF 50, 100 and 200 mg / kg administration groups, -49.19,- 54.87, 0.39, -36.61, -53.44 and -70.48%.

The composition-administered group of the present invention comprising β-glucan and extract from the extract showed a dose-dependent decrease in blood AST content and amount of change. On the other hand, the lateral single-body administration group showed a change in blood AST content very similar to the medium control group.

Furthermore, the composite composition of the present invention showed a better inhibitory effect on blood AST content increase than each single composition dose group of the same dose, which demonstrates the synergistic effect of the composite composition according to the present invention. It is also an excellent inhibitory effect on the increase in blood AST content comparable to silymarin (SILY), which is widely used as a treatment for liver disease.

Blood ALT  Effect on concentration

Abbreviations are as defined in Table 1. In the table, 1) Change I: change in ALT concentration over the period of administration of the composition of the present invention (from day 0 to sacrifice); *: P <0.01 and; compared to Sham control by MW test; #, ##: p <0.01 and p <0.05, respectively, compared to the medium control group by MW test.

As shown in Table 8, the media control group showed a significant (p <0.01) increase in the blood ALT (GPT) content compared to the normal group. Decrease in (p <0.01 or p <0.05) blood ALT content was recognized after the end of dosing. At the time of final necropsy, the blood ALT content was 1188.38% in the medium control group compared to the normal group, and -13.80, -14.39, 0.47 in the SILY, sPOL, sFME, MPF 50, 100 and 200 mg / kg administration groups, respectively. , -12.58, -15.92 and -18.97%.

Furthermore, a significant (p <0.01 or p <0.05) decrease in blood ALT content over the administration period was also observed in all dose groups except for the lateral unilateral single composition dose group. In the 1: 4 combination composition group, the dose-dependent blood ALT content and the amount of change were decreased. On the other hand, the lateral single-body administration group showed a change in blood ALT content very similar to the medium control group. The change in blood ALT content during the administration period was 3397.14% in the medium control group compared to the normal group, and in the SILY, sPOL, sFME, MPF 50, 100 and 200 mg / kg administration groups, -28.10,- 29.74, 0.33, -25.49, -35.54 and -38.64%.

The composition of the present invention comprising β-glucan and extract from the extract showed a superior inhibitory effect on blood ALT content increase over each single composition administration group at the same dose, demonstrating the synergistic effect of the composite composition according to the present invention. It is also an excellent inhibitory effect on the increase in blood ALT content comparable to silymarin (SILY), which is widely used as a treatment for liver disease.

Example  3-5 hyperlipidemia treatment effect

Low Density Lipoprotein (LDL), High Density Lipoprotein (HDL), Triglyceride, and total cholesterol (T-CHOL) concentrations are representative indicators for measuring hyperlipidemia and its extent, expressed in mg / dl. Blood was collected from the orbital vein and the abdominal vein, respectively, on day 21 of administration of STZ (day 0 of administration) and on day 28 after administration of the composition of the present invention, and plasma was isolated according to a known method. HDL, LDL, triglyceride and T-CHOL concentrations in isolated plasma were measured using an automated blood analyzer (Toshiba 200FR, Japan) as recommended by the user. The results are summarized in Tables 9-12, respectively.

Abbreviations are as defined in Table 1. In Tables 9 to 12, 1) Change I: change in concentration of each indicator during the administration period of the composition of the present invention (from day 0 to sacrifice); *, **: p <0.01 and; compared with Sham control by MW test; #, ##: p <0.01 and p <0.05, respectively, as compared to the medium control group by the MW test.

Blood HDL  Effect on concentration

As shown in Table 9, the media control group showed a significant (p <0.01) decrease in blood HDL content compared to the normal group. A relatively significant (p <0.01 or p <0.05) increase in blood HDL content was recognized after the end of the administration. At the time of final necropsy, the blood HDL content was -58.91% in the medium control group compared to the normal group, and in the SILY, sPOL, sFME, MPF 50, 100 and 200 mg / kg groups, 35.85, 49.69, 1.89, 35.85, 44.65 and 54.09% change.

Furthermore, a significant (p <0.01 or p <0.05) increase in blood HDL content over the administration period was also observed in all dosing groups, except for the lateral unilateral single composition and SILY administration group. On the other hand, the lateral single-body administration group showed a change in blood HDL content very similar to that of the medium control group, while the SILY-administered group was not significant, but a significant increase in blood HDL content and change amount was recognized. The change in blood HDL content during the administration period was -264.10% in the medium control group compared to the normal group, and in the SILY, sPOL, sFME, MPF 50, 100 and 200 mg / kg administration groups, respectively, 91.63, 127.56 , 4.12, 97.88, 116.63 and 133.81%.

Compositions of the present invention comprising β-glucan and extract of extract showed a better inhibitory effect on blood HDL content reduction than each single composition administration group at the same dose, demonstrating the synergistic effect of the composite composition of the present invention. It also exhibits an excellent similar blood HDL content reduction inhibitory effect comparable to SILY, which is widely used as a treatment for hyperlipidemia.

Effect on blood LDL levels

As shown in Table 10, the media control group showed a significant (p <0.01) increase in blood LDL content compared to the normal group. A significant (p <0.01 or p <0.05) decrease in blood LDL content was recognized. At the time of final necropsy, the blood LDL content was 216.22% in the medium control group compared to the normal group, and -17.09, -21.37, 0.85 in the SILY, sPOL, sFME, MPF 50, 100 and 200 mg / kg administration groups, respectively. , -16.24, -19.66 and -24.79%.

Furthermore, a significant (p <0.01 or p <0.05) decrease in blood LDL content during the administration period was also observed in all the administration groups except the epithelial single composition group. On the other hand, the lateral single-body administration group showed a change in blood LDL content very similar to the medium control group. The change in blood LDL content during the administration period was 628.57% in the medium control group compared to the normal group, and in the SILY, sPOL, sFME, MPF 50, 100 and 200 mg / kg administration groups, -37.25,- 47.06, 3.92, -39.22, -35.29 and -54.90%.

Compositions of the present invention comprising β-glucans and extracts showed superior inhibitory effect on blood LDL content increase over each single composition dose group at the same dose, demonstrating the synergistic effect of the composite compositions of the present invention. It also shows an excellent similar blood LDL content increase inhibitory effect comparable to SILY, which is widely used as a treatment for hyperlipidemia.

Effect on blood triglyceride concentration

As shown in Table 11, the media control group was found to have a significant (p <0.01) increase in blood triglyceride content compared to the normal group, but after the end of the administration, all the administration groups except the epithelial single composition administration group were compared with the media control group. Significant (p <0.01 or p <0.05) decreases in blood triglyceride content were recognized. At the time of final necropsy, the blood triglyceride content was 1730.57% in the medium control group compared to the normal group, and in the SILY, sPOL, sFME, MPF 50, 100 and 200 mg / kg groups, -29.13, -30.63,- Changes of 1.16, -28.08, -26.41, and -37.16%.

Furthermore, a significant (p <0.01 or p <0.05) decrease in blood triglyceride content over the administration period was also observed in all dose groups except for the lateral and single composition dose groups. On the other hand, the lateral single-body administration group showed a change in blood triglyceride content very similar to the medium control group. The change in blood triglyceride content during the administration period was 2858.62% in the medium control group compared to the normal group, and in the SILY, sPOL, sFME, MPF 50, 100 and 200 mg / kg administration groups, -59.03,- 65.97, 0.41, -58.80, -53.73 and -744.80%.

Compositions of the present invention comprising β-glucan and extract of extract showed a superior inhibitory effect on blood triglyceride content increase over each single composition dose group at the same dose, demonstrating the synergistic effect of the composite compositions of the present invention. It also shows an excellent similar blood triglyceride content reduction effect comparable to SILY, which is widely used as a treatment for hyperlipidemia.

Effect on blood T-CHOL concentration

As shown in Table 12, the media control group was found to have a significant (p <0.01) increase in blood T-CHOL content compared to the normal group, but it was significant in all the administration groups except the lateral mononuclear group. (p <0.01 or p <0.05) A decrease in blood T-CHOL content was recognized after the end of the administration. At the final necropsy, the blood T-CHOL content was 77.52% in the medium control group compared to the normal group, and -12.66, -17.18 in the SILY, sPOL, sFME, MPF 50, 100 and 200 mg / kg groups, respectively. , -1.29, -11.50, -16.80 and -20.41%.

Furthermore, a significant decrease in the amount of T-CHOL content in the blood during the administration period was also observed in all the administration groups except for the lateral mononuclear administration group compared to the medium control group. The dose-dependent dose of the 1: 4 combination composition showed a decrease in blood T-CHOL content and change. On the other hand, the lateral single-body administration group showed a change in blood T-CHOL content very similar to the medium control group. The change in blood T-CHOL content during the administration period was 110.26% in the medium control group compared to the normal group, and -131.71 in the SILY, sPOL, sFME, MPF 50, 100 and 200 mg / kg administration groups, respectively. , -157.32, -9.54, -103.66, -159.76 and -193.90%.

The composition of the present invention comprising β-glucan and extract of extract showed a superior inhibitory effect on blood T-CHOL content increase over each single composition administration group at the same dose, demonstrating the synergistic effect of the composite composition of the present invention. . It also exhibits an excellent similar inhibitory effect of increasing HDL content in blood comparable to SILY, which is widely used as a treatment for hyperlipidemia.

Example  4. Effects on Histopathological Changes in Kidney and Liver

Example  4-1 Histological Analysis Methods

Liver was harvested at the end of administration of each group administered STZ rats with the composite composition of the present invention and the drug used as a control according to Example 2. The extracted liver was fixed in formalin buffered at 10% neutral pH, embedded in paraffin according to a known method, cut into 3-4 μm thick sections, stained with Hematoxylin and Eosin (H & E), and then automated image analyzer. Analyzes were performed using (analySIS Image Processing; SIS, Germany).

Specifically, in the liver, the degenerated hepatic parenchyma site (denoted as PDR in Table 13 below) and the fibrosis site (indicated as PFR in Table 13 below) present in the portal triad, in%, per hepatic parenchyma. Indicated.

In the case of kidneys, the number (N) of the tubules contracted per 100 tubules in the renal parenchyma and degenerative changes including spheronization characteristics were counted and expressed as N / 100 tubules (indicated by NAT in Table 13 below). In addition, the number (N) of glomeruli in which capillary dilatation atrophy changes per 100 glomeruli in the renal parenchyma was expressed as N / 100 glomeruli (indicated by NAG in Table 13 below). The results are shown in Table 13, FIGS. 1 and 2.

All data are expressed as mean ± standard deviation. The number of individuals in each dosing group was 6 and statistical analysis was performed using SPSS (Release 6.1.3., SPSS Inc., USA) for Windows as Mann-Whitney U-Wilcoxon Rank Sum W test (MW test). .

Abbreviations are as defined in Table 1 and Example 4-1. *, **: p <0.01 and p <0.05, respectively, compared to the Sham control by MW test; #, ##: p <0.01 and p <0.05, respectively, as compared to the medium control group by the MW test.

Example  4-2 Effects on Histopathological Changes in Kidneys

The results are in FIG. 1 and Table 13 above. In the STZ animal model before administration of the composite composition of the present invention, some fibrotic findings were recognized along with renal interstitial atrophy, glomerular capillary dilatation, tubular atrophy, and cell necrosis in typical diabetic nephropathy (FIG. 1 c, d).

After administration of the composite composition of the present invention, a significant increase in degeneration site, tubules and glomeruli was observed in the media control group, but in all the administration groups except for the lateral unilateral single composition administration group, significant (p <0.01 or p <0.05) degeneration was found in the media control group. Reductions in site, tubule and glomeruli were shown, respectively. The composite composition administration group of the present invention showed a dose-dependent reduction in kidney lesions. On the other hand, hepatic histopathologic findings of the renal lateral single composition administration group were very similar to that of the medium control group.

The renal degeneration rate was 1331.67% in the medium control group compared to the normal group, and in the CAPT, sPOL, sFME, MPF 50, 100 and 200 mg / kg administration groups, respectively, -41.83, -44.37, -0.23,- 27.49, -40.93 and -55.86%.

The number of denatured tubules was 418.57% in the media control group compared to the normal group, and -44.35, -47.11, 0.28,-in the CAPT, sPOL, sFME, MPF 50, 100 and 200 mg / kg administration groups, respectively. 37.74, -45.18 and -67.22%.

The number of degenerative glomeruli was 986.05% in the medium control group compared to the normal group, and in the CAPT, sPOL, sFME, MPF 50, 100 and 200 mg / kg administration groups, respectively, -38.12, -52.68, 3.21,- 27.62, -51.39 and -72.59%.

The above results show that the composite composition of the present invention exhibits an inhibitory effect on the increase of histopathological lesions of the kidneys than the administration group of each single composition of the same dose, demonstrating the synergistic effect on the diabetic nephropathy of the composite composition of the present invention. It is consistent with the BUN and creatinine test results. In addition, the therapeutic effect of nephropathy by the complex composition of the present invention is an excellent effect comparable to the effect of CAPT widely used as a therapeutic agent for diabetic nephropathy.

Furthermore, as shown in Figure 1, compared with the kidney tissue of the normal group (a, b), STZ rats (50 mg / kg (k, l), 100 mg / kg (m, n) administered the composite composition of the present invention ) And 200 mg / kg (o, p)) showed histological findings that were nearly normal compared to rats that were not administered (media controls, c, d). This proved that the composite composition of the present invention has an excellent effect on nephropathy. In addition, the results are excellent effects comparable to the effect of CAPT (e, f) administration widely used as a therapeutic agent for nephropathy.

Example  Effect on Liver Pathologic Changes in 4-3 Liver

The results are in FIG. 2 and Table 13 above. In the STZ animal model prior to administration of the composite composition of the present invention, local fibrosis was observed in typical liver disease (c, d of FIG. 2).

After administration of the composite composition of the present invention, an increase in the fibrosis site was recognized in the media control group, but all the administration groups except the epicondyle single composition administration group showed significant decreases in lesions (p <0.01 or p <0.05), respectively, compared to the media control group. It was. The composite composition administration group of the present invention showed a dose-dependent decrease in liver lesions. The hepatic histopathologic findings of the hepatic lateral single composition administration group were very similar to that of the medium control group.

The hepatic fibrosis site was 371.69% in the media control group compared to the normal group, and in the SILY, sPOL, sFME, MPF 50, 100 and 200 mg / kg administration groups, respectively, -44.60, -45.61, -2.59,- Changes of 32.35, -43.39 and -51.84% were shown.

The results indicate that the composite composition of the present invention exhibits an inhibitory effect on the increase of histopathologic lesions of the new kidney than that of each single composition-administered group at the same dose, demonstrating the synergistic effect on the diabetic nephropathy of the composite composition of the present invention. It is consistent with the BUN and creatinine test results. In addition, the therapeutic effect of the liver disease by the composite composition of the present invention is an excellent effect comparable to the effect of SILY widely used as a therapeutic agent for liver disease.

Further, as shown in Figure 2, compared with the liver tissue of the normal group (a, b), STZ rats (50 mg / kg (k, l), 100 mg / kg (m, n) administered the composite composition of the present invention ) And 200 mg / kg (o, p)) showed close histological findings in the livers of nearly normal rats, compared to unadministered rats (media controls, c, d). This proved that the composite composition of the present invention has an excellent effect on hepatopathy. In addition, the result is an excellent effect comparable to the effect of SILY (e, f) administration widely used as a therapeutic agent for liver disease.

Furthermore, no abnormal syndromes (hair loss, gastrointestinal disorders, hypoglycemia, etc.) did not appear in the animal model during the experimental period. From this, it could be confirmed that the combination of β-glucan and extract from the extract was not particularly toxic to the animal model.

Taken together, all of the above results demonstrate that the combination of β-glucan and leprosy extract of the present invention have an excellent effect on the treatment of this metabolic syndrome, and at the same time show a synergistic effect of treatment, compared with the use of each alone. By doing so, it indicates that the composition of the present invention containing these as an active ingredient can be effectively used as a therapeutic agent for metabolic syndrome.

Β-1,3 / 1,6-glucan and baekbaek extract prepared in Example 1 may be administered in the following formulation, the following formulation is only to illustrate the present invention is limited to the contents of the present invention It is not. Β-glucan and the extract of the following examples can be added in an appropriate weight ratio within the range of 1:10 to 10: 1, preferably mixed in a weight ratio of 1: 4.

Formulation example  1. Preparation of Tablets

β-1,3 / 1,6-glucan

And whitening extract 200mg

Lactose 100mg

Starch 100mg

Magnesium stearate proper amount

Tablets were prepared by mixing and tableting the above components according to a conventional tablet production method.

Formulation example  2. Preparation of Capsule

 β-1,3 / 1,6-glucan

And whitening extract 100mg

Lactose 50mg

Starch 50mg

Talc 2mg

Magnesium stearate proper amount

According to the conventional capsule preparation method, the above ingredients were mixed and filled into gelatin capsules to prepare capsules.

Formulation example  3. Liquid  Produce

β-1,3 / 1,6-glucan

And whitening extract 1000mg

20 mg of sugar

Isomerized sugar 20mg

Lemon flavor

Purified water was added to make a total of 1000 ml. According to the conventional method for preparing a liquid, the above components were mixed, and then filled into a brown bottle and sterilized to prepare a liquid.

Formulation example  4. Preparation of Injectables

 β-1,3 / 1,6-glucan

And whitening extract 100mg

Sodium metabisulfite 3.0mg

Methylparaben 0.8mg

Propylparaben 0.1mg

Appropriate sterile distilled water for injection

The above components were mixed and prepared in a conventional manner so that the final volume was 2 ml, and then filled into 2 ml ampoules and sterilized to prepare an injection.

Formulation example  5. Manufacture of health drinks

 β-1,3 / 1,6-glucan

And whitening extract 1000mg

Citric acid 1000mg

Oligosaccharide 100g

Mesyl Concentrate 2g

* 163 g of taurine

Add 900 ml of purified water

After mixing the above components in accordance with a conventional healthy beverage production method, and stirred and heated at 85 ℃ for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2L container, sealed sterilized and then refrigerated and stored in the present invention Used to prepare healthy beverage compositions.

Formulation example  6. Manufacture of healthy food

 β-1,3 / 1,6-glucan

And whitening extract 1000mg

Vitamin mixture proper amount

Vitamin A Acetate 70μg

Vitamin E 1.0mg

Vitamin B1 0.13mg

Vitamin B2 0.15mg

Vitamin B6 0.5mg

0.2 μg of vitamin B12

Vitamin C 10mg

Biotin 10μg

Nicotinic Acid 1.7mg

Folic acid 50μg

Calcium Pantothenate 0.5mg

Vitamin E 1.0mg

Mineral mixture

Ferrous Sulfate 1.75mg

Zinc Oxide 0.82mg

Magnesium Carbonate 25.3mg

15 mg potassium monophosphate

Dicalcium Phosphate 55mg

Potassium Citrate 90mg

Calcium Carbonate 100mg

Magnesium chloride 24.8mg

The composition ratio of the above-mentioned vitamin and mineral mixtures is composed of relatively suitable ingredients suitable for health foods in a preferred manufacturing example, but the compounding ratios may be arbitrarily modified, and the above ingredients are mixed according to a conventional health food manufacturing method. Health foods of granule formulations were prepared.

The composition comprising the β-glucan and extract of the extract of the present invention not only has a superior therapeutic effect on nephropathy and hepatopathy due to hypoglycemia and diabetes, but also has a synergistic effect compared to the use of each component alone, Side effects due to the use of the extract alone can be significantly lowered, and can effectively treat metabolic syndrome by replacing conventional individual therapeutic agents.

Claims (12)

β-, comprising a glucose main chain linked by a bond, wherein at least one of the glucose is β-1,3 / 1,6-glucan linked by branched glucose with a β-1,6 bond Pharmaceutical composition for treating metabolic syndrome comprising glucan and baekbaek extract as an active ingredient. delete The composition of claim 1, wherein the β-glucan is β-1,3 / 1,6 glucan of Formula 1 below: [Formula 1]

[Wherein n is 1 to about 4,000 and X is lactic acid, maleic acid or sulfoacetic acid] The composition of claim 1, wherein the β-glucan is derived from Aureobasidium pullulans SM2001. 2. The composition of claim 1, wherein the metabolic syndrome has symptoms comprising one or more of glucose intolerance, complications caused by glucose tolerance, hypertension, and hyperlipidemia. 6. The composition according to claim 5, wherein the complication due to glucose tolerance is nephropathy, hyperlipidemia or hepatopathy. 7. The composition of any one of claims 1 or 3 to 6, wherein the weight ratio of β-glucan to extract is about 1: 4. β-, comprising a glucose main chain linked by a bond, wherein at least one of the glucose is β-1,3 / 1,6-glucan linked by branched glucose with a β-1,6 bond Health functional foods for improving the symptoms of metabolic syndrome comprising glucans and extracts as extracts. delete According to claim 8, β-glucan is a functional food for improving the symptoms of metabolic syndrome, characterized in that β-1,3 / 1,6 glucan of the formula (1):

[Wherein n is 1 to about 4,000 and X is lactic acid, maleic acid or sulfoacetic acid] 9. The dietary supplement for metabolic syndrome symptom improvement according to claim 8, wherein the β-glucan is derived from Aureobasidium pullulans SM2001. 12. The dietary supplement for metabolic syndrome symptom according to any one of claims 8 to 10, wherein the weight ratio of β-glucan to extract is about 1: 4.

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