JP5118316B2 - Obesity prevention / amelioration agent - Google Patents

Description

  The present invention relates to an obesity preventive or ameliorating agent that has an effect of preventing or ameliorating obesity and is useful as a pharmaceutical and a food.

  In recent years, in addition to the excessive intake of energy (increased intake of fat and sucrose) accompanying the Westernization of Japanese dietary habits, exercise deficits overlap and lifestyle-related diseases such as obesity and diabetes continue to increase. Yes. From this social background, obesity prevention and improvement measures are extremely important.

  In order to prevent and ameliorate obesity, intake of a low-calorie diet or a low-fat diet is a method generally proposed by dietitians. In recent years, water-insoluble dietary fibers such as wheat bran, water-soluble dietary fibers such as indigestible dextrin, and digestion-resistant starches such as high amylose starch have promoted lipid excretion (for example, see Non-Patent Document 1) and sugar absorption. It has an inhibitory action (for example, see Non-Patent Document 2), a blood neutral fat lowering action (for example, see Non-Patent Document 3), or a glucose tolerance improving action (for example, Non-Patent Document 4, Patent Document 5 and Non-Patent Document 6) have been reported, and are considered effective in preventing or improving obesity.

  In addition, since a rapid increase in blood lipids after meals is thought to promote fat accumulation, an approach to suppress postprandial hyperlipidemia (increase in blood triglycerides) in the prevention and improvement of obesity. In recent years, chitansan gum, alginic acid propylene glycol ester (for example, see Patent Document 1) and chitosan (for example, see Patent Document 2) have been reported as safe and effective lipid absorption inhibitors.

  However, the above-mentioned low-calorie diet or low-fat diet may have some temporary effects on weight loss, but it is rejected by the person after a long period of time due to the monotonous flavor of the food that makes it. It is difficult to maintain this for a long time. Moreover, in order for food materials, such as the said conventional water-insoluble dietary fiber, water-soluble dietary fiber, and digestion-resistant starch, to express said physiological effect, it must continue ingesting a high dose for a long period of time. Moreover, even if the physiological action is expressed, suppression of obesity has not been confirmed. Furthermore, when foods and drinks are produced using them, it is often difficult to contain them in foods in sufficient amounts because they often impair the texture of foods and drinks, such as appearance, taste, texture, and smoothness. However, there are problems that application fields are limited, and that it is difficult to continue taking such foods and drinks for a long time.

On the other hand, glycogen is a polysaccharide in which D-glucose is polymerized by glycoside bonds having many branches to form a dendritic structure, and is known as a storage polysaccharide in animals and plants. In recent years, glycogen having a molecular weight of 3,000 to 9,500 has an effect of improving endurance and an effect of suppressing an increase in blood lactate after exercise (Patent Document 3), and glycogen derived from sweet corn has an antitumor effect. It is known that potato-derived glycogen promotes growth of juvenile shrimp, and the growth rate of lactic acid bacteria is increased (Non-patent document 8). It has been reported that it is used in cosmetics (Non-patent Document 9).
However, it has not been known so far that glycogen has an effect of preventing or improving obesity.

JP-A-5-186356 JP-A-3-290170 JP 2005-213185 A Am J Clin Nutr 1978 31 (10 Suppl): 521-529 Journal of the Japan Endocrine Society 1992 68 (6): 623-35 Am J Clin Nutr 1989 49 (2): 337-44 Acta Paediatr Hung 1985 26 (1): 75-7 J Endocrinol 1995 144 (3): 533-8 Am J Clin Nutr 1989 49 (2): 337-44 Junichi Sasaki et al., Journal of BCG / BRM Therapy Study Group, 27-31, vol27, 2003 Kazuyoshi Matsunaga (Bizen Kasei), Journal pf Applied Glycoscience, 37, vol52,2005 Satoshi Hiramatsu et al., FRAGRANCE J, 49-54, vol3, 1998

  The present invention relates to providing a drug or food that exhibits an excellent effect in preventing or improving obesity and has high safety.

  As a result of searching for materials having physical properties different from dietary fibers represented by conventional indigestible starch, cellulose, and indigestible dextrin, the present inventors have found that glycogen suppresses visceral fat accumulation with a slight intake. The present invention has been found to be useful as a pharmaceutical and food material having an obesity-inhibiting action such as enhancement of lipid combustion and exhibiting an effect of preventing and improving obesity.

  That is, the present invention relates to an agent for preventing or improving obesity containing glycogen as an active ingredient, an agent for suppressing visceral fat accumulation, an agent for enhancing lipid metabolism, an agent for enhancing lipid combustion, and an agent for preventing or improving hyperglycemia due to obesity.

  In addition, the present invention relates to a food which is characterized by having glycogen as an active ingredient and has an effect of preventing or improving obesity, and which is labeled for use in preventing or improving obesity.

  The obesity prevention or amelioration agent of the present invention has an excellent obesity prevention or amelioration action, and thus prevention or improvement of hyperlipidemia, prevention or improvement of hyperglycemia, prevention of heart diseases such as heart failure, thrombosis It is considered useful for prevention or improvement of various lifestyle-related diseases such as prevention of colon cancer and rectal cancer. Therefore, it is useful as a pharmaceutical or functional food for preventing, treating or improving such symptoms and diseases.

  The glycogen used in the present invention may be any of animal origin, plant origin (phytoglycogen), fungi / bacteria / yeast. Examples of animals include shellfish such as scallops, abalone, oysters, mussels, and turban shells, and livers of cattle and pigs. Examples of plants include seeds such as corn, barley and rice. Of these, phytoglycogens such as corn, barley, and rice are preferable, and phytoglycogens derived from sweet corn are particularly preferable from the viewpoint of ease of purification, content, price, and the like. Generally, the molecular weight of glycogen is said to be about 1 million to several million (Chemical Dictionary 3 Reprinted Edition, Kyoritsu Shuppan, Tokyo, 1963, p90), but lower molecular weight of about 100,000 to 800,000. Plant-derived glycogen (derived from sweet corn) has also been reported (Hiramamatsu et al., Fragrance Journal 1998 (3), 49-54), and any molecular weight glycogen can be used in the present invention.

The glycogen used in the present invention can be obtained, for example, by extraction from animals or plants, fungi, bacteria, yeast, etc. containing glycogen. Extraction may be carried out by using a general glycogen extraction method (Biochemical Experiment Course 4, Carbohydrate Chemistry (above), edited by the Japanese Biochemical Society, published by Tokyo Kagaku Dojin, 1976, P128-129). It is not necessarily limited to this method. Alternatively, the raw material may be pulverized or directly immersed in water or a solvent containing water (for example, dilute trichloroacetic acid aqueous solution, potassium hydroxide aqueous solution, acetic acid aqueous solution, sodium hydroxide aqueous solution, etc.). It can also be extracted using boiled juice from animals and plants containing glycogen. The dipping time can be changed depending on the pretreatment conditions such as the pulverization status of the raw materials and the step of obtaining the broth. After the immersion treatment, the supernatant is collected by appropriate means such as natural sedimentation, centrifugation, and filtration. The obtained supernatant can be freeze-dried to obtain crude glycogen. Further, the supernatant is used as it is or crude glycogen is subjected to general purification as required to obtain glycogen having a high degree of purification. Moreover, after processing a raw material with a proteolytic enzyme, it can obtain by gel filtration and ion exchange chromatography.
Commercially available sweet corn-derived phytoglycogens can also be used.

As will be described later in Examples, glycogen has an obesity-inhibiting action in which body weight and visceral fat amount are significantly reduced, and has an action of enhancing lipid burning amount and promoting fatty acid oxidation activity. Therefore, glycogen is used as an obesity preventing or improving agent, visceral fat accumulation inhibitor, lipid metabolism enhancing agent, lipid burning enhancing agent, or an agent for preventing or improving hyperglycemia due to obesity (hereinafter also referred to as obesity preventing or improving agent). It can be used, and can also be used for producing the obesity prevention or amelioration agent and the like.
Such an obesity prevention or amelioration agent is used to prevent or improve obesity, such as hyperlipidemia, hyperglycemia, heart disease such as heart failure, thrombosis, hypertension, fatty liver and other symptoms or diseases caused by obesity. It can be used as a human or veterinary drug, quasi-drug, or food that can exert effects such as prevention or improvement.
In addition, the obesity prevention or amelioration agent is based on the concept of prevention or improvement of obesity, body fat accumulation suppression, etc., and cosmetics, beauty foods, foods for the sick, foods for specified health use, etc., which are indicated as necessary. It can be used as a functional food.

  Examples of the dosage form when the agent for preventing or improving obesity of the present invention is used as a pharmaceutical include oral solid preparations such as tablets and granules, and oral liquid preparations such as oral liquids and syrups. When preparing an oral solid preparation, an excipient, if necessary, a binder, a disintegrant, a lubricant, a coloring agent, a corrigent, a flavoring agent and the like are added to the glycogen of the present invention, followed by a conventional method. Thus, tablets, coated tablets, granules, powders, capsules and the like can be produced. Moreover, when preparing a liquid preparation for oral use, a liquid preparation, a syrup, an elixir, etc. can be manufactured by a conventional method by adding a corrigent, a buffer, a stabilizer, a corrigent and the like.

In the case where the obesity prevention or ameliorating agent of the present invention is used as a food, it can be used for various foods such as breads, cakes, noodles, confectionery, jelly, frozen foods, ice creams, dairy products, and beverages. , And the same forms (tablets, capsules, syrups, etc.) as the above-mentioned preparations for oral administration.
To prepare various forms of food, glycogen alone or other food ingredients, solvents, softeners, oils, emulsifiers, preservatives, fragrances, stabilizers, colorants, UV absorbers, antioxidants An agent, a humectant, a thickener and the like can be used in appropriate combination.

  The blending amount of glycogen to be blended in each of the above preparations is usually 5 to 100% by mass, preferably 20 to 100% by mass, and more preferably 30 to 100% by mass.

  The dose (effective intake) of the agent for preventing or improving obesity of the present invention is preferably 0.01 g / kg body weight or more per day, particularly 0.1 g / kg body weight or more, and more preferably 0.4 g / kg body weight. The above is preferable.

Test Example 1 Obesity preventive effect, visceral fat accumulation inhibitory effect 1-1 Test meal The composition of the test meal (powder meal) is shown in Table 1. The low fat diet was 5% TG (triglyceride), and the high fat diet was 30% lipid (5% lard + 25% TG).
Glycogen-containing foods were 5%, 10% and 28.5% of glycogen in high fat foods.
Glycogen in the test meal is derived from sweet corn (manufactured by Kewpie), lard, casein, cellulose, AIN76 mineral mixture, AIN76 vitamin mixture, pre-gelatinized potato starch is manufactured by Oriental Yeast Co., Ltd., and sucrose is Wako Pure Chemical Industries, Ltd. ) Sucrose fine granules (special grade) were used. The used fats and oils (TG) are a mixture of hyrinol safflower oil, rapeseed oil, and sesame oil, and the main constituents of fatty acids are oleic acid, linoleic acid, α-linolenic acid, and palmitic acid.

1-2 Test animals and their breeding
7-week-old male mice C57BL / 6J Jcl (CLEA Japan) were reared on a normal diet (CRF-1: manufactured by Oriental Yeast Co., Ltd.) for 1 week, then grouped so that the initial body weight was almost constant at 8 weeks of age. Started. The mice were bred in 5 cages and 2 cages (N = 10) for each test food group. Feeding was free intake using Roden Cafe (manufactured by Oriental Yeast Co., Ltd.) and replaced with a new test meal every 2-3 days. The test food was subdivided in advance for 2 to 3 days and refrigerated at 4 ° C. until use. For water supply, tap water was freely consumed using a dedicated water supply.

1-3 Collection of blood and visceral fat On the last day of the experiment, the blood and visceral fat were collected as shown below under non-fasting conditions. The mouse was immediately opened under anesthesia, blood was collected from the abdominal vena cava, and the blood was killed. Further, visceral fat (peri-testicular fat, perirenal fat, retroperitoneal fat, mesenteric fat) was collected, weighed, and the total value was calculated as visceral fat mass. Using a portion of the collected blood, the blood glucose level was immediately measured using a simple blood glucose meter (glucose dehydrogenase / potentiometric method, manufactured by Roche Diagnostik).

1-4 Aggregation method, statistical test method
Because of the group breeding of 5 animals / cage, it was counted except for 2 animals that had been fighting with each other during the 15-week breeding period and found sudden and sudden weight loss.
Furthermore, Fisher's r-z test was used for the correlation between the amount of glycogen and the body weight and visceral fat, and t-test was used for comparison between the glycogen-containing diet and the high fat diet (control).

1-5 Results The results are shown in Table 2. By raising for 15 weeks, it was found that the high-fat diet (control) increased body weight and visceral fat mass compared to the low-fat diet and became obese.
There was a tendency for the body weight, visceral fat mass, blood glucose level, and insulin level to all decrease as the amount of glycogen added increased. In the correlation test (Fisher's z test), a negative correlation was found between the amount of glycogen and the body weight, visceral fat content, and blood glucose level after 15 weeks of breeding.
In addition, as a result of the suppression of obesity, it is considered that the blood sugar level of the glycogen combination diet group was reduced.

Test Example 2 Enhancement of Lipid Burning Amount 2-1 Test Food Table 3 shows the composition of the test food (powdered food). The high fat diet was 30% lipid (5% lard + 25% TG). The glycogen combination diet was a high fat diet with 28.5% glycogen.
Glycogen in the test meal is derived from sweet corn (manufactured by Kewpie), lard, casein, cellulose, AIN76 mineral mixture, AIN76 vitamin mixture, pre-gelatinized potato starch is manufactured by Oriental Yeast Co., Ltd., and sucrose is Wako Pure Chemical Industries, Ltd. ) Sucrose fine granules (special grade) were used. The used fats and oils (TG) are a mixture of hyrinol safflower oil, rapeseed oil, and sesame oil, and the main constituents of fatty acids are oleic acid, linoleic acid, α-linolenic acid, and palmitic acid.

2-2 Method
C57BL / 6J mice (♂, 8 weeks old, 10 animals / group) were allowed to eat the test food freely and were kept in the metabolic chamber (Columbus Oxymax system) for 90 hours and evaluated for energy metabolism by breath analysis. It was. Oxygen consumption (VO ₂ ) and carbon dioxide emission (VCO ₂ ) were measured every 18 minutes, and the respiratory quotient and the amount of lipid burning (mg / kg body weight / minute) were calculated according to the usual method.

2-3 Results Table 4 shows the results.
During the breeding period in the metabolic chamber, there was no significant difference in the amount of food consumed between the control diet group and the glycogen combination diet group.
As a result of analyzing the respiratory quotient and the amount of lipid combustion by repeated two-way ANOVA, the glycogen combination group had a significantly lower respiratory quotient than the control food group (p <0.001), and the lipid combustion amount was significantly higher. High (p <0.001). From this result, it can be seen that the lipid burning is enhanced in the glycogen-containing diet.

Test Example 3 Liver Lipid Metabolism Enhancement Effect As in Test Example 1, use 10 test mice (powdered food) prepared in the composition shown in Table 1 with 10 mice (C57BL / 6J ♂, 7 weeks old) per group. And raised. After 4 weeks of breeding, the mice were sacrificed under anesthesia, and the livers were removed. Liver fatty acid oxidation activity was measured according to a conventional method.
From the results in Table 5, it can be seen that mice fed glycogen have high fatty acid oxidation activity in the liver and increased lipid metabolism.

Claims (5)

An obesity-preventing or ameliorating agent (excluding foods) containing glycogen as an active ingredient and containing 20 to 100% by mass of glycogen in the preparation. A visceral fat accumulation inhibitor (excluding foods) containing glycogen as an active ingredient and containing 20 to 100% by mass of glycogen in the preparation. A lipid metabolism-enhancing agent (excluding foods) containing glycogen as an active ingredient and containing 20 to 100% by mass of glycogen in the preparation. A lipid combustion enhancer (excluding foods) containing glycogen as an active ingredient and containing 20 to 100% by mass of glycogen in the preparation. An agent for preventing or improving hyperglycemia due to obesity (excluding foods), comprising glycogen as an active ingredient and containing 20 to 100% by mass of glycogen in the preparation.