KR20120061019A - Composition for prevention and treatment of obesity and metabolic diseases comprising selenomethionine - Google Patents

Abstract

PURPOSE: A pharmaceutical composition and health functional food containing selenomethionine are provided to prevent and treat obesity and lipid-related metabolic diseases. CONSTITUTION: A pharmaceutical composition for preventing and treating obesity and lipid-related metabolic diseases contains selenomethionine as an active ingredient. The pharmaceutical composition is manufactured in the form of powder, granules, tablets, capsules, suspension, emulsion, syrup, suppository, or sterilized injection solution. Selenomethionine suppresses differentiation of adipocyte. A health functional food contains selenomethionine as an active ingredient. The health functional food is used in the form of capsules, tablets, granules, powder, or beverage.

Description

Composition for prevention and treatment of obesity and metabolic diseases comprising selenomethionine

The present invention relates to a pharmaceutical composition and health functional food for the prevention and treatment of obesity and lipid-related metabolic diseases containing selenomethionine as an active ingredient.

In addition to the development of the industry, the shift to instant food consumption and meat-based eating has become a major cause of the increase in the obese population. Obesity is caused by adipocyte differentiation due to hormonal changes and disproportionate energy metabolism due to excessive fat intake. Adipogenesis in the body is caused by the differentiation of fat cells from preadipocytes. As a process of accumulation, mature adipocytes are differentiated from immature adipocytes, such as fibroblasts, and eventually form lipid droplets within the cells. As such, the accumulation of fat and excess energy during fat cell differentiation not only leads to obesity, but also metabolic syndrome in which various lipid-related metabolic diseases such as diabetes, hyperlipidemia, arteriosclerosis, hypertension, cardiovascular disease, or multiple occurrences of these diseases simultaneously It is known to be a major cause. Metabolic syndrome refers to a syndrome that is accompanied by risk factors such as hyperlipidemia, hypertension, abnormal glucose metabolism, and obesity. Recently, the Adult Treatment Program III (ATP III), established by the World Health Organization and the National Institute of Health's Cardiopulmonary Blood Research Institute, was officially named as metabolic syndrome or insulin resistance syndrome.

The differentiation process of adipocytes has been studied using cells such as 3T3-L1, and various transcription factors, particularly transcription factors known to be involved in localization, CAAT enhancer binding proteins (C / EBPs), It is known that PPARs (Peroxisome Proliferator Activated receptor) and ADD / SREBPs (Adipocyte determination and differentiation dependent factor1 / sterol response element binding proteins) are expressed over time and regulate the process (Bart A Jessen et al., Gene, 299, pp95-100, 2002; Darlington et al., J. Biol. Chem., 273, pp30057-30060, 1998; Brun RP et al., Curr. Opin. Cell. Biol., 8, pp826-832 , 1996). Given the stimulation of hormones such as isobutylmethylxanthin, dexamethasone and insulin (MDI), C / EBP β and δ are the first, transiently expressed, to initiate differentiation into adipocytes (Reusch J. E et al., Mol Cell Biol., 20, pp 1008-1020, 2000). This continues to lead to increased expression of C / EBPa and PPARγ (James M. N. et al., J. Nutr., 130, pp 3122S-3126S, 2000). PPARγ is a particularly important transcription factor for adipocyte differentiation, and is present in the promoters of various adipocyte genes after forming dimers with the retinoic acid X receptor protein (RXR). Binds to peroxisome proliferator response elements (PPRE) (Tontonoz PE et al., Genes Dev., 8, pp1224-1234, 1994;

Hwang, C. S et al., Cell Dev. Biol., 13, pp 873-877). The interaction of PPARγ with C / EBPa is critical for differentiation into mature adipocytes, which regulate the expression of adipocyte specific proteins and fat metabolizing enzymes, such as fatty acid binding protein aP2. In addition, ADD1 / SREBPs play an important role in fat metabolism, but are also known to be involved in the differentiation process. Expression of ADD1 / SREBP1c in immature adipocytes is believed to contribute to the activation of PPARγ (Rosen ED et al., Annu. Rev. Cell Dev. Biol., 16, pp 145-171, 2000; Osborn TF, J. Biol Chem., 275, pp 32379-32382, 2000). Only the differentiated fat cells synthesize fatty acids and store triglycerides.

Therefore, the current research trend is focused on the discovery of substances that can inhibit metabolic processes related to adipocyte differentiation as a method for preventing or treating obesity and lipid-related metabolic diseases. For example, Korean Patent No. 10-0798004 has revealed the action of inhibiting adipocyte differentiation of a compound isolated from the gourd plant extract, and Korean Patent No. 10-0813222 shows the action of inhibiting adipocyte differentiation of herbal extracts. Revealed.

Seleno amino acid is an amino acid containing selenium (Se), the most commonly seen and the most widely studied forms are selenomethionine (selenomethionine), selenocycteine, selenomethionine (selenomethionine). Selenomethionine is the most common form of selenium, the most common form of selenium, and in a 1970 study by Olsen et al., About 50 percent of wheat is this type of selenium, and in the 2000 study of the mouth, 85 percent of selenium-rich yeast was selenium. It is called.

Therefore, the present inventors continued to study the substances effective for obesity and lipid-related metabolic diseases, and completed the present invention by releasing selenomethionine to inhibit the differentiation of hormone-induced adipocytes.

An object of the present invention is to provide a pharmaceutical composition and health functional food for the prevention and treatment of obesity and lipid-related metabolic diseases containing selenomethionine effective in inhibiting adipocyte differentiation.

In order to achieve the above object, the present invention provides a pharmaceutical composition for the prevention and treatment of obesity and lipid-related metabolic diseases containing selenomethionine as an active ingredient. The metabolic disease may be, for example, diabetes mellitus, hyperlipidemia, arteriosclerosis, hypertension, cardiovascular disease or metabolic syndrome in which the diseases occur simultaneously, and the composition may be in capsule, tablet, granule, powder or beverage form. Do. In another aspect, the present invention provides a pharmaceutical composition for the prevention and treatment of obesity and lipid-related metabolic diseases, characterized in that the selenomethionine inhibits the differentiation of adipocytes.

Furthermore, the present invention provides a dietary supplement for the prevention and symptom relief of obesity and lipid-related metabolic diseases, containing selenomethionine as an active ingredient. The metabolic disease may be, for example, diabetes, hyperlipidemia, arteriosclerosis, hypertension, cardiovascular disease, or metabolic syndrome in which the diseases occur simultaneously. In another aspect, the present invention provides a dietary supplement for the prevention and symptom relief of obesity and lipid-related metabolic diseases, characterized in that the selenomethionine inhibits the differentiation of adipocytes.

The composition of the present invention, the selenomethionine relative to the total weight of the composition 0.1 to 50% by weight. The composition comprising selenomethionine of the present invention may further comprise a suitable carrier, excipient or diluent according to conventional methods. Carriers, excipients and diluents that may be included in the compositions of the present invention 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 compositions according to the invention can be used in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral formulations, external preparations, suppositories or sterile injectable solutions, respectively, according to conventional methods. have. Specifically, when formulated, it may be prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrating agents, surfactants, and the like. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations include at least one excipient such as starch, calcium carbonate, sucrose, and the like in the selenomethionine. It can be prepared by mixing sucrose, lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate, talc can also be used. Liquid preparations for oral use include suspensions, solvents, emulsions, and syrups, and include various excipients such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. Can be. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations and suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

The present invention may vary depending on the age, sex and weight of the patient, but in general, an amount of 0.01 to 500 mg / kg, preferably 0.1 to 100 mg / kg, may be administered once to several times a day. . The dosage may also be increased or decreased depending on the route of administration, the severity of the disease, sex, weight, age, and the like. Thus, the dosage amounts are not intended to limit the scope of the invention in any manner.

The composition of the present invention can be administered to mammals such as rats, mice, livestock, humans, and the like by various routes. All modes of administration can be envisaged, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection. Selenomethionine of the present invention has little toxicity and side effects, and therefore can be used with confidence even for prolonged administration for prophylactic purposes.

The present invention provides a health functional food comprising the selenomethionine and a food supplement acceptable food supplement, various foods, for example, beverages, gums, tea, vitamin complexes, health supplements, etc. It may be used in the form of a powder, granule, acupuncture, tablet, capsule or beverage. In this case, the amount of the selenomethionine in the food or beverage can generally be added as 0.01 to 15% by weight of the total food weight in the case of the health food composition of the present invention, 0.02 to 10 based on 100 ml for the health beverage composition g, preferably 0.3 to 1 g.

Food additives as defined herein include food additives customary in the art, such as flavorings, flavors, colorants, fillers, stabilizers, and the like. The health beverage composition according to the present invention is an essential ingredient in the indicated ratio, and there is no particular limitation on the ingredients added in addition to the selenomethionine, and may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks. . Examples of the natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; Polysaccharides such as dextrin, cyclodextrin; Conventional sugars such as 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 (e.g., Rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. have. 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, 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 beverages, and the like. In addition, the compositions of the present invention 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 proportion of such additives is not so critical, but is generally selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.

As described above, the selenomethionine according to the present invention is excellent in inhibiting the adipocyte differentiation, it can be used as a pharmaceutical composition and health functional food for the prevention and treatment of obesity and lipid-related metabolic diseases containing it as an active ingredient have.

1 is a photograph of comparison with a microscope after staining with oil red O when treated with selenomethionine to hormone-induced differentiated adipocytes.
Figure 2 is a graph measuring the lipid content when treated with selenomethionine to hormone-induced differentiated adipocytes.

Hereinafter, the present invention will be described in detail by the following examples. However, the following examples are merely to illustrate the invention, but the content of the present invention is not limited by the following examples.

Manufacturing example  One. Selenomethio  Preparation of Sample

Selenomethionine was purchased from LKT Laboratories Inc. and used. The selenomethionine was dissolved in dimethyl sulfoxide (DMSO) at a concentration of 100 mM / L to form a high concentration solution, and then diluted in a culture solution so as to have a DMSO content of 0.1% or less and treated to cells.

Example  One. Selenomethionine  Inhibitory Activity of Adipocyte Differentiation

Hormone mixture (10 μg / ml insulin, 0.5 mM 3-isobutyl-1-methylxanthine, and 1 μg / ml dexamethasone) into adipocyte progenitor 3T3-L1 cells (purchased from the American Tissue Culture Collection, USA) Was treated by mixing in a culture medium and then cultured for two days, 10 μg / ml of insulin was mixed in the culture medium, and then cultured for two days, and finally, the culture medium was treated with two days to induce adipocyte differentiation.

The selenomethionine sample obtained in the above preparation was treated at a concentration of 10 μM from the initial stage of induction of adipocyte differentiation, and then the inhibitory activity of adipocyte differentiation was compared with the control group not treated with selenomethionine. After staining with Oil Red O (ORO) and observed under a microscope (see Fig. 1) was confirmed the degree of inhibition of adipocyte differentiation quantitatively by measuring the lipid content (see Fig. 2).

As a result, it was confirmed that selenomethionine effectively inhibited adipocyte differentiation as shown in FIG. 1. As shown in Figure 2 when treated with selenomethionine decreased about 43%, it can be seen that the inhibitory activity of adipocyte differentiation was effectively inhibited.

Example  2. PPARs Measurement of activation activity

In order to investigate whether selenomethionine can modulate the activity of peroxysomal proliferation receptors (PPARs), the following experiment was performed. CV-1 cells were transformed with only the tkPPRE luciferase reporter plasmid, the reporter plasmid and the vector expressing PPAR alpha, beta, or gamma, and then treated after 24 hours, and harvested after 24 hours. Luciferase activity was measured. In the case of PPAR alpha, fibrate (F6020-100G) was treated at a concentration of 100 uM. For beta and delta, GW501516 was used at a concentration of 100 uM. For gamma, troglitazone (T2573) was used. Used at a concentration of 100 uM. As a result, selenomethionine showed significant activity.

Examples of preparations for the compositions of the present invention are illustrated below. However, the following formulation example only illustrates this invention, The content of this invention is not limited by the following formulation example.

Formulation Example 1 Preparation of Powder

Selenomethionine 300 mg

Lactose 100 mg

Talc 10 mg

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

Formulation Example 2: Preparation of Tablet

Selenomethionine 50 mg

Corn starch 100 mg

Lactose 100 mg

2 mg magnesium stearate

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

Formulation Example 3 Preparation of Capsule

Selenomethionine 50 mg

Corn starch 100 mg

Lactose 100 mg

2 mg magnesium stearate

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

Formulation Example 4 Preparation of Injection

Selenomethionine 50 mg

Appropriate sterile distilled water for injection

pH adjuster

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

Formulation Example 5 Preparation of Liquid

Selenomethionine 100 mg

10 g of isomerized sugar

5 g of mannitol

Purified water

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

Formulation Example 6 Preparation of Healthy Food

Selenomethionine 1000 mg

Vitamin mixture proper amount

70 μg of Vitamin A Acetate

Vitamin E 1.0 mg

Vitamin B1 0.13 mg

Vitamin B2 0.15 mg

Vitamin B6 0.5 mg

0.2 μg of vitamin B12

Vitamin C 10 mg

10 μg biotin

Nicotinic Acid 1.7 mg

50 μg folic acid

Calcium Pantothenate 0.5mg

Mineral mixture

Ferrous Sulfate 1.75 mg

Zinc Oxide 0.82 mg

Magnesium carbonate 25.3 mg

Potassium monophosphate 15 mg

Dibasic calcium phosphate 55 mg

Potassium Citrate 90 mg

Calcium Carbonate 100 mg

Magnesium chloride 24.8 mg

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

Formulation Example 7 Preparation of Healthy Drinks

Selenomethionine 1000 mg

Citric acid 1000 mg

100 g oligosaccharides

Plum concentrate 2 g

1 g of taurine

Add 900 ml of purified water

After mixing the above components according to a conventional healthy beverage manufacturing method, and then stirred and heated at 85 ° C. for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 l container, sealed sterilized and then refrigerated and stored in the present invention For the preparation of healthy beverage compositions.

Although the compositional ratio is relatively mixed with a component suitable for a favorite drink, it is also possible to arbitrarily modify the compounding ratio according to the regional or national preference such as the demand class, the demanding country, and the use purpose.

Claims (8)

Pharmaceutical composition for the prevention and treatment of obesity and lipid-related metabolic diseases containing selenomethionine as an active ingredient.
The method of claim 1,
The metabolic disease is at least one disease selected from the group consisting of diabetes, hyperlipidemia, arteriosclerosis, hypertension, cardiovascular disease or metabolic syndrome in which the diseases occur simultaneously, prevention and treatment of obesity and lipid-related metabolic diseases Pharmaceutical composition for.
The method of claim 1,
The composition is a capsule, tablets, granules, powders or drinks in the form of a pharmaceutical composition for the prevention and treatment of obesity and lipid-related metabolic diseases.
The method of claim 1,
The selenomethionine is a pharmaceutical composition for preventing and treating obesity and lipid-related metabolic diseases, characterized in that it inhibits the differentiation of adipocytes.
A dietary supplement for the prevention and symptom relief of obesity and lipid-related metabolic diseases, containing selenomethionine as an active ingredient.
6. The method of claim 5,
The metabolic disease is diabetes or hyperlipidemia, arteriosclerosis, hypertension, cardiovascular disease or at least one disease selected from the group consisting of metabolic syndrome that occurs in the multiple, obesity and lipid-related metabolic disease prevention and symptomatic relief Dietary supplements.
6. The method of claim 5,
The health functional food is a capsule, tablets, granules, powder or a beverage, characterized in that obesity and lipid-related metabolic disease prevention and symptomatic health functional food.
6. The method of claim 5,
The selenomethionine is a health functional food for preventing and alleviating symptoms of obesity and lipid-related metabolic diseases, characterized in that it inhibits the differentiation of fat cells.

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