KR101271538B1 - Composition for prevention and improvement of obesity comprised of organic acid, L-carnitine, L-arginine and nicotinamide - Google Patents

Abstract

The present invention relates to a food composition or a pharmaceutical composition for preventing and improving obesity comprising an organic acid, L-carnitine, L-arginine, and nicotinamide as active ingredients. The composition of the present invention has the effect of reducing the accumulation of fat in the body, particularly in the blood, liver and adipose tissue, and reduce the differentiation of adipocytes, according to the organic acid, L-carnitine, L- arginine and nicotinamide It provides a use of the composition of the present invention containing as having the effect of preventing and improving obesity.

Description

Composition for prevention and improvement of obesity comprising of organic acid, L-carnitine, L-arginine and nicotinamide}

The present invention relates to a food composition or pharmaceutical composition for the prevention and improvement of obesity comprising an organic acid, L-carnitine, L-arginine and nicotinamide as an active ingredient.

As the mortality rate of adult diseases has increased recently, attention has been focused on obesity. As a result, various health supplements with anti-obesity effects have been released in Korea as well as in the global pharmaceutical industry. As the lack of exercise becomes more severe, obesity increases rapidly, and the increase in adult disease is a social problem. Also, as the dietary life of the Korean people is westernized, chronic lifestyle diseases such as adult diseases are increasing. As the aging society enters, the demand for silver foods for the elderly is expected to increase.

Obesity occurs when excessive energy accumulates due to metabolic imbalance when the supply is much greater than the demand for energy. Clinically, it is involved in the development of various diseases or worsens diseases. , Diabetes, fatty liver and cholelithiasis. In particular, women with endometrial cancer, gallbladder cancer, cervical cancer, ovarian cancer, and breast cancer frequently occur, and in the case of endometrial cancer, an increase in the incidence and mortality caused by obesity is reported to be most significant compared to other cancer diseases. It is also reported that obesity is more than 1.3 times higher than normal weight in mortality.

Chiazolidinedione-based drugs and biguanides, which reduce insulin resistance, aimed at improving obesity and conducted long-term clinical trials on obese patients with metabolic syndrome. Antiobesity medications include Xenical (Orlistat) and Reductil (Sibutramine). However, these drugs have anti-obesity effects due to the mechanism of appetite suppression and fat absorption inhibition rather than promoting the burning and decomposition of fat, and serious side effects have been reported, and there is no clear guarantee on safety. Therefore, there is a need to develop a new material that is equivalent to or higher than the conventional material but more safe for the human body.

An object of the present invention is to examine the effects of preventing and improving obesity of a composition that can improve obesity by decomposing and removing body fat, particularly abdominal fat, which is over-formed by using a substance that breaks down fat and promotes combustion. Based on culture experiments, serum analysis (total cholesterol, triglyceride (TG), glucose) and liver analysis (total lipid, cholesterol, triglyceride) and weight changes and weight changes of liver and adipose tissue were measured. It is to provide a use as a food composition for the prevention and improvement of obesity.

Another object of the present invention to provide a pharmaceutical composition for the prevention and improvement of obesity is mild, high safety based on the animal experiment and cell culture experiment.

The composition for preventing and improving obesity according to the present invention may be characterized by comprising lemon concentrate, L-carnitine, L-arginine and nicotinamide as active ingredients.

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In addition, the composition for preventing and improving obesity is 80 to 95% by weight of lemon concentrate, 1 to 10% by weight of L-carnitine, 1 to 3% by weight of L-arginine, 0.01 to 0.2% by weight of nicotinic acid amide relative to 100% by weight of the composition. It may be characterized in that it comprises 1 to 10% by weight of purified water.

In addition, the composition for preventing and improving obesity may be characterized in that the dietary supplement, a health functional food or a food composition that is a food additive.

In addition, the composition for preventing and improving obesity may be characterized in that the pharmaceutical composition further comprises a pharmaceutically acceptable carrier.

The composition of the present invention comprising lemon concentrate, L-carnitine, L-arginine and nicotinamide as effective ingredients has the effect of reducing the accumulation of fat in the body, particularly in the blood, liver and adipose tissue, and reducing the differentiation of adipocytes. Seemed.

Accordingly, the composition of the present invention comprising a lemon concentrate, L-carnitine, L-arginine and nicotinamide as an active ingredient provides a use of the prevention and improvement effect of obesity.

In addition, the composition of the present invention is a safe substance formed from natural substances, so the composition of the present invention can be used as a food composition or pharmaceutical composition for the prevention and improvement of obesity is very useful industrially.

1 is a table summarizing the results by Experimental Examples 1 to 3 of the present invention.
Figure 2a is a graph comparing the weight change during the four weeks by Experimental Example 1 of the present invention.
Figure 2b is a graph comparing the final weight change by Experimental Example 1 of the present invention.
Figure 2c is a graph comparing the weight change of the liver according to Experimental Example 1 of the present invention.
Figure 2d is a graph comparing the weight change of kidney fat according to Experimental Example 1 of the present invention.
Figure 2e is a graph comparing the weight change of epididymal fat according to Experimental Example 1 of the present invention.
Figure 3a is a graph comparing the total lipid content in liver tissue according to Experimental Example 2 of the present invention.
Figure 3b is a graph comparing the cholesterol content in liver tissue according to Experimental Example 2 of the present invention.
Figure 3c is a graph comparing the triglyceride content in liver tissue according to Experimental Example 2 of the present invention.
Figure 4a is a graph comparing the cholesterol content in serum by Experimental Example 3 of the present invention.
Figure 4b is a graph comparing the triglyceride content in serum by Experimental Example 3 of the present invention.
Figure 4c is a graph comparing the glucose content in serum by Experimental Example 3 of the present invention.
5 is a graph comparing the degree of fat differentiation according to Experimental Example 4 of the present invention.

The present inventors have shown that fruit concentrates containing large amounts of various organic acids, including citrate, which act as important mediators in energy metabolic pathways, have anti-obesity effects, such as L-carnitine, L-arginine and nicotinamide. In order to verify the hypothesis that by administering together with these agents, the basal metabolic rate of such a bioactive substance may be increased, and as a result, the synergy effect on the biological activity of the substance may be exhibited. The present invention was completed by orally administering the composition of the present invention together with a high fat diet in a rat to establish an indicator for improving obesity.

The present invention relates to a composition for the prevention and improvement of obesity comprising an organic acid, L-carnitine, L- arginine and nicotinamide as an active ingredient.

Organic acids are abundant in fruits, and the main components of fruits related to acidity in flavours include malic acid, citric acid, fish acid, iso citric acid, and succinic acid. Especially citric acid is contained in lemon or citrus fruits, and TCA cycle (TriCarboxylic Acid Cycle) Citric acid plays an important role in the body's energy metabolism.

L-carnitine is a substance known as an essential nutrient for normal energy generation and fat metabolism of the human body.L-carnitine is a nutrient that plays an important role in converting fat into an energy source.L-carnitine deficiency reduces the concentration of fatty acids in the mitochondria. This also reduces energy production. In addition, CPT-1 (Carnitine palmitoyltransferase 1) using L-carnitine as a substrate has been shown to act as a rate limiting enzyme for fatty acid oxidation among various enzymes involved in fatty acid oxidation (Eaton, Prog Lipid Res 41 (3). ): 197-269, 2002).

L-arginine is one of the amino acids that make up the protein and belongs to the protein protamine in fish sperm. As a semi-essential amino acid required for the growth of children or animals, it has been reported that ingestion of L-arginine promotes the release of glucagon, which directly accelerates the breakdown of adipose tissue in the human body (Kalkhoff RK, et al. N Engl J Med 289: 465-467).

Nicotinamide is an essential ingredient for the growth and energy generation of vitamin B3, which enhances the function of beta cells, and is used for the treatment and prevention of diabetes.

Extraction method of the active ingredient used in the present invention can be used by appropriately selecting and applying a method commonly known in the art.

In the present invention, the organic acid is characterized in that the lemon concentrate containing the organic acid, the lemon concentrate is characterized in that it comprises 80 to 95% by weight relative to 100% by weight of the composition of the present invention.

In addition, the present invention comprises 1 to 10% by weight of L-carnitine, 1 to 3% by weight of L-arginine, 0.01 to 0.2% by weight of nicotinic acid amide, and 1 to 10% by weight of purified water, based on 100% by weight of the composition. do.

When in the above content range, the composition of the present invention may exhibit a synergistic effect on the effect of improving obesity by increasing the basal metabolic efficiency.

The composition of the present invention is preferably in the form of a powder or liquid, and the method of preparing the lemon concentrate is not particularly limited, but a mixture of lemon powder and extracts which have been juiced, filtered, vacuum concentrated and / or lyophilized, is used. It is desirable to.

The composition of the present invention may be characterized in that the food composition is a dietary supplement, health functional food or food additives. The composition of the present invention may be prepared in the form of tea, juice and drink and consumed, or may be consumed by granulation, encapsulation and powdering.

In addition, the composition of the present invention can be prepared in the form of a mixed composition with known ingredients known as auxiliaries for enhancing the effect of obesity. The auxiliary agent is not particularly limited, but vitamin C, trehalose, flavor liquid (lemon), complex golden extract, animal extract powder (placental) and the like may be used alone or in combination.

The composition of the present invention may be characterized as being a pharmaceutical composition further comprising a pharmaceutically acceptable carrier. The pharmaceutical composition may be prepared in an oral dosage form (tablets, suspensions, granules, emulsions, capsules, syrups, etc.), including pharmaceutically acceptable carriers, excipients, etc. in addition to the active ingredient.

Hereinafter, the present invention will be specifically described by way of Examples and Experimental Examples.

< Example >

A total of 48 male SD rats were used to investigate the effects of the composition of the present invention on lipid metabolism of high fat diet-induced obese animals. After eight groups were grouped for four weeks, the experimental diet was prepared as shown in Table 1.

Ingredients (grams) Normal diet Highland method Casein 200.0 200.0 Sucrose 100.0 50.0 Dextrose 132.0 132.0 Corn Starch 398.0 155.0 Cellulose 50.0 50.0 Soybean oil 70.0 25 Lard 0 175 L-Cystine 3.0 3.0 Choline bitartrate 2.5 2.5 tert-Butylhydroquinone 0.014 0.014 Mineral mix * 35.0 35.0 Vitamin mix * 10.0 10.0 Myo-inositol 0 0 Chicory dietary fiber 0 0 Energy (kcal) 4,000 4,776 Protein (% of energy) 20 24 Carbohydrate
(% of energy) 64 41 Fat (% of energy) 7 24

Mineral mixture and vitamin mixture were based on the AIN-93G formulation.

1) AIN-93G Mineral Mixture (g / kg): CaCO3 357, K2HPO4 196, C6H5K3O7xH2O 70, NaCl 74, K2SO4 46, MgO 24, Iron Citrate 6, ZnCO3 1.7, MgCO3 0.63, Cu (CO3) 2 0.3, Phosphorus Iodide 0.01, sodium selenite 0.01, ammonium paramolybdate 4H2O 0.008, sodium metasilicate 9H2O 1.45, chromium phosphate 12H2O 0.28, LiCl 0.02, bile acid 0.08, sodium fluoride 0.06, Ni (CO3) 2 0.03, ammonium vanadate 0.007, fine powder Sugar 221.

2) AIN-93G vitamin mixture (g / kg): Niacin 3, calcium pantothenate 1.6, pyridoxine hydrochloride 0.7, thiamine hydrochloride 0.6, riboflavin 0.6, folic acid 0.2, biotin 0.02, vitamin E acetic acid (500 IU / g) 15, vitamin B12 (0.1%) 2.5, Vitamin A palmitate (500,000 IU / g) 0.8, Vitamin D3 (400,000 IU / g) 0.25, Vitamin K1 / Dextrose Mix (10 mg / g) 7.5, Sugar 967.

< Experimental Example  1> Investigation of weight loss effect and weight change of liver and adipose tissue of the composition of the present invention

The weight loss effect and weight change of the liver were investigated using the composition of the present invention. The experimental results were expressed as mean ± standard deviation using SAS program, and post-verification was performed using Duncan's multiple range test at the significance level of p <0.05 to analyze significant statistical differences between groups. .

In the control group, only purified water was orally administered to the normal diet, and in the high fat diet (HFD) group, only purified water was orally administered to the high fat diet, and the test group was divided into four groups. One of the samples was continuously orally administered 1 ml daily.

① Administration of the sample {composed of 88% by weight of lemon concentrate and 12% by weight of purified water} on a high fat diet (hereinafter referred to as "HFD + OA")

② administration of the sample (composed of 3.847% by weight of L-carnitine and 96.153% by weight of purified water) on a high fat diet (hereinafter referred to as "HFD + L-Car"),

③ Administration of a sample (composition of 2% by weight of L-arginine, 0.116% by weight of nicotinamide, and 97.884% by weight of purified water) to a high fat diet (hereinafter referred to as "HFD + L-Arg + Nico")

④ The composition of high-fat diet {conjugated with lemon concentrate 88% by weight, L-carnitine 3.847% by weight, L-arginine 2% by weight, nicotinamide 0.116% by weight, purified water 6.037% by weight] composition of the present invention} HFD + OA + L-Car + L-Arg + Nico ".)

Body weight change was measured weekly, and after 4 weeks, the weight change and the liver and adipose tissue were extracted before and after the experiment, and the weight change was analyzed. Feed intake was the same between treatment groups.

As shown in FIG. 1 and FIG. 2A, as the time passed, all groups showed weight gain, and began to show significant difference from 2 weeks after the start of salary. Four weeks after the start of the experiment, the high-fat diet group showed the highest increase, and the group receiving the composition of the present invention showed the lowest increase, showing similar results to the control group.

As shown in Figures 1 and 2B, changes in each group of body weight showed the highest weight gain in the high-fat diet group and obesity except for the HFD + L-Arg + Nico group when the sample was administered to a high fat diet. Among them, the group that received the composition of the present invention (HFD + OA + L-Car + L-Arg + Nico) had the highest offsetting effect.

As shown in Figure 1 and 2c, liver weight changes also significantly increased compared to the control diet according to the high-fat diet, and reduced the weight gain of the liver when administering the sample to the high-fat diet, the composition of the present invention The group receiving the showed the greatest reduction effect.

As shown in Figure 1 and 2d, the change in the weight of the kidney fat tissue significantly reduced the weight of kidney fat tissue when the sample is administered on a high fat diet, especially the group receiving the composition of the present invention the largest reduction It showed an effect.

As shown in Figure 1 and 2e, the weight change of the epididymal adipose tissue also significantly reduced the weight of the epididymal adipose tissue when the sample was administered on a high fat diet, especially the group receiving the composition of the present invention the largest reduction It showed an effect, and also there was no significant difference with the control.

As described above, the composition of the present invention significantly reduced the weight of the high fat diet-induced rats and the weight of liver and adipose tissue, thereby confirming a synergistic effect on the reduction of body fat mass.

< Experimental Example  2> Investigation of lipid, cholesterol, triglyceride changes in liver tissue according to the feeding of the composition of the present invention

On the fourth week after the experiment, all rats were fasted for one day, and then the liver tissue was extracted and rapidly frozen with liquid nitrogen and stored at -70 ° C until analysis.

To analyze lipid content, triglyceride and cholesterol content in liver tissue of each experimental group, extracted with nucleic acid: isopropanol (3: 2 v / v), suspended in 0.1% Triton X-100 after nitrogen concentration, and analyzed automatically Using a kit (Asan Pharmaceutical, Korea) was analyzed by PRIME automatic analyzer (Asan Pharmaceutical), TBARS Masugi et al. The FAS activity was measured using the method of Martyn et al.

As shown in Figure 1 and Figure 3a, the total lipid content in liver tissue significantly increased according to the high-fat diet, liver tissue when the sample was administered to the high-fat diet except the HFD + L-Arg + Nico group The accumulation of lipids in the liver was reduced, and organic acids were more effective than L-carnitine in lipid accumulation in liver tissue, and the group receiving the composition of the present invention showed the lowest result.

As shown in Figures 1 and 3b, the cholesterol content in liver tissue was also significantly increased according to the diet of the high fat diet, and when the sample was administered to the high fat diet, the accumulation of cholesterol in the liver tissue was reduced, The group receiving the composition had the lowest result.

As shown in Figures 1 and 3c, the triglyceride content in the liver tissue was highest in the high fat diet group, the triglyceride content was reduced when the sample was administered to the high fat diet, HFD + OA group, HFD + L-Car group There was no significant difference between the and HFD + L-Arg + Nico group, but the group receiving the composition of the present invention was found to be significantly reduced.

As described above, in the biochemical indicators in liver tissue, the composition of the present invention has a result of offsetting fat accumulation in liver tissue, which may be related to weight and liver and adipose tissue results.

< Experimental Example  3> Changes in blood cholesterol, triglyceride content and glucose levels according to the feeding of the composition of the present invention

The blood collected after dissection of the experimental animals was centrifuged at 3000 rpm for 10 minutes to obtain serum and stored at -70 ℃ until analysis, blood cholesterol, triglycerides and glucose levels were analyzed using Cobas c111 analyzer.

As shown in Figures 1 and 4a, the blood cholesterol content increased by the high-fat diet was significantly reduced at the time of sample administration, among which the group receiving the composition of the present invention showed the lowest result.

As shown in Figure 1 and Figure 4b, the triglyceride in the blood increased by the high-fat diet was significantly reduced when the sample administration, it was found that the organic acid and L-carnitine showed an effect on the reduction of triglycerides, the present invention The group receiving the composition of showed the highest reduction.

As shown in Figures 1 and 4c, the blood glucose content increased by the high-fat diet was significantly reduced when the sample was administered, the effect of reducing by the organic acid was high, the group receiving the composition of the present invention was highest A decrease was shown.

As described above, the composition of the present invention in blood biochemical markers has resulted in reducing obesity-causing factors in the blood.

< Experimental Example  4> 3 according to the treatment of the composition of the present invention T3 - L1  Investigation of the differentiation inhibitory effect of adipocytes

3T3-L1 adipocytes (purchased from ATCC) were replaced with 70% fusion (DMEM) with DMEM (Dulbecco's Modified Eagle's Medium, Gibco 1210-0038) medium containing 10% calf serum. incubated in a 10% CO ₂ incubator until confluent.

Differentiation into adipocytes resulted in 10% fetal bovine serum, 0.5 mM 3-isobutyl-1-methyxanthine, 1 μM dexamethasone and 167 nM insulin. After 48 hours of incubation in the medium, the medium was replaced with DMEM medium containing 10% fetal bovine serum and 167 nM insulin (insulin) for another 48 hours.

Finally, the cultured cells were further cultured for 48 hours in a medium containing only 10% fetal bovine serum to obtain differentiated adipocytes.

Differentiated adipocytes were cultured in medium containing 5% nonfatty bovine serum for 16 hours, then washed three times with PBS (Phosphate buffer saline) the following day. ① caffeine 0.05 and 0.2 mg / ml, ② lemon concentrate 0.1 mg / ml, ③ L-carnitine 0.1 mg / ml, ④ L-arginine 0.1 mg / ml + nicotinamide 0.1 mg / ml, ⑤ lemon concentrate 0.1 mg / ml + L-carnitine 0.1 mg / ml + L-arginine 0.1 mg / ml + 0.1 mg / ml mixture of nicotinamide were treated respectively.

Each test substance was treated with medium exchange every 48 hours, and the amount of triglyceride was measured by oil red o staining after 8 days, and the result of the measurement was shown in FIG. Was used.

As shown in Figure 5, the inhibition of adipocyte differentiation by lemon concentrate, L-carnitine, or L-arginine + nicotinamide treatment was significantly reduced compared to the control, but its efficacy was less than the positive control.

When mixed with lemon concentrate, L-carnitine, L-arginine, and nicotinamide, the result was similar to that of the positive control, and the differentiation of adipocytes was suppressed by about 60%. It was confirmed that the effective suppression.

Claims (5)

Lemon concentrate, L-carnitine, L- arginine and nicotinamide composition for the prevention and improvement of obesity, characterized in that it comprises as an active ingredient.
delete The method of claim 1,
The composition for preventing and improving obesity is 80 to 95% by weight of lemon concentrate, 1 to 10% by weight of L-carnitine, 1 to 3% by weight of L-arginine, 0.01 to 0.2% by weight of nicotinic acid amide, purified water Obesity prevention and improvement composition comprising 1 to 10% by weight. The method according to claim 1 or 3,
The composition for preventing and improving obesity is a composition for preventing and improving obesity, characterized in that the food composition is a dietary supplement, health functional food or food additives. The method according to claim 1 or 3,
The composition for preventing and improving obesity is a composition for preventing and improving obesity, characterized in that the pharmaceutical composition further comprises a pharmaceutically acceptable carrier.

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