JP4723320B2 - Blood leptin level increasing agent - Google Patents

Description

  The present invention relates to a system for preventing and / or treating obesity and / or diabetes containing uridylic acid, uridine and uracil as active ingredients.

  Along with the westernization of eating habits and lifestyles, lifestyle-related diseases such as diabetes are rapidly increasing. According to a survey conducted in August 2003, the number of people who are worried about diabetes is estimated to reach about 16 million people, including those who are strongly suspected of having diabetes and who cannot be denied.

  Types of diabetes can be broadly divided into type 1 diabetes (insulin-dependent), which loses insulin secretion in the pancreas, and type 2 diabetes (insulin-independent) due to decreased insulin secretion or decreased insulin sensitivity in each tissue. It is done.

  Asians, including Japanese, have low insulin secretion ability and are prone to diabetes, mainly insulin secretion disorders. On the other hand, Westerners are considered to develop remarkable obesity due to their high insulin secretion ability, and to develop diabetes due to insulin resistance.

  Currently approved oral diabetes drugs in Japan include sulfonylurea drugs, sulfonamide drugs, fast-acting insulin secretagogues, thiazolidine drugs, biguanides, and α-glucosidase inhibitors. Blood glucose levels are controlled by methods such as promoting insulin secretion from the pancreas, improving insulin resistance in each tissue, and suppressing carbohydrate absorption in the intestine. All drugs are known to have serious side effects such as liver damage with a low probability, and safer drugs or materials are required.

  Recently, new approaches such as a method of administering leptin, a hormone secreted from fat cells, and a method of selectively inhibiting sugar uptake (SGLT1) in the intestinal tract (Kissei Pharmaceutical Co., Ltd., Dainippon Pharmaceutical Co., Ltd.) Drugs for the treatment of diabetes have been developed.

  Leptin is a hormone secreted by fat cells in the body and acts on the hypothalamus to suppress appetite and increase energy consumption.

  Leptin has the effect of reducing the fat content in the liver and skeletal muscles, mainly via the central nervous system, and acting directly on pancreatic β cells to reduce lipotoxicity and improve insulin resistance and insulin secretion, It is expected for clinical application as a therapeutic agent for various types of diabetes.

  In obesity (type 2 diabetes), leptin alone is ineffective because of its resistance to leptin. However, it has been clarified that when used in combination with weight loss treatment such as calorie restriction, the improvement of glucose tolerance and insulin resistance is promoted.

  It has been found that the amount of insulin necessary for treatment can be reduced by leptin even in insulin secretion-lowering diabetes (type 1 diabetes).

  Blood free fatty acid (NEFA) concentration is an index of lipid metabolism abnormality and shows a high value in diabetes. NEFA itself is considered to be an exacerbation factor of diabetes because it increases insulin resistance in each tissue.

On the other hand, some nucleic acid-related substances such as nucleosides and nucleotides are known to be useful as seasonings and pharmaceuticals (see, for example, Non-Patent Document 1), but the use of uridylic acid alone suppresses obesity and diabetes. It is not known to be useful, and even more, there has been no report that these effects have been confirmed using actual rats.
Biotechnology Encyclopedia, CMC Corporation, October 9, 1986, pp.246-247

  The present invention has been made for the purpose of developing a system for preventing and / or treating obesity and / or diabetes, and a highly safe new system using natural products.

  In order to solve the above-mentioned problems, the present inventors examined the effect of oral administration of uridylic acid on sugar metabolism and lipid metabolism, and uridylic acid increased leptin concentration, and blood glucose, insulin, NEFA It was found that the concentration and the TG (triglyceride) concentration in the liver were decreased.

The present invention was finally completed as a result of further research based on these useful new findings, and an agent for preventing / treating obesity / diabetes comprising at least one of uridylic acid, uridine, and uracil as an active ingredient. This is a basic technical idea.
Hereinafter, the present invention will be described in detail.

  In the present invention, a nucleic acid-related compound having uracil as a base is used as an active ingredient, and examples of the nucleic acid-related compound include at least one selected from uracil, uridine, and uridylic acid.

  The origin of the nucleic acid-related compound is not particularly limited and may be a synthetic product, but those derived from natural products such as enzymes, bacteria, milk, seafood, animals and plants are preferred. The method for purifying nucleic acid-related compounds is not particularly limited, and a completely purified product can be used as well as a crude product or a contained product. A liquid or suspension-treated product can be widely used.

  The present invention has a great feature in that the effectiveness (that is, functionality, physiological activity or physiological action) of uridylic acid was directly confirmed using an actual rat. Specifically, after uridylic acid was orally administered to rats, body weight measurement, blood collection, tissue collection was performed, analysis was performed on these biological samples, and various physiological actions were actually and directly confirmed. It is not a nucleic acid related compound derived from other bases, and it is extremely characteristic in that it was actually confirmed that it is effective only with uridylic acid, not in combination with nucleic acid related compounds derived from other bases. Is.

  According to the present invention, the above-described nucleic acid-related compound as an active ingredient, pharmaceuticals for humans or non-human animals, foods and drinks, supplements, prepared milk powder, enteral nutrition, health foods and drinks, feed additives, feeds, etc. It can be put to practical use as various types of compositions. The administration method may be oral administration, intravenous administration, or direct administration to the affected area.

  The compounding amount of the active ingredient may be arbitrary, but may be appropriately determined according to the purpose of use (prevention, health, or treatment), patient age, administration method, dosage form, etc. A range of% is suitable. However, when ingested for the purpose of health or health maintenance over a long period of time, the amount may be smaller than the above range, and since this active ingredient has no safety problem, Even if it is used in large quantities, there is no problem. As a result of a 10-day acute toxicity test using mice, no death was observed even at an oral dose of 1000 mg / kg.

  When using it as a food or drink (including supplements, functional foods such as foods for specified health use and functional nutritional foods), use this active ingredient (including inclusions and processed products) as is, It can be used in accordance with conventional methods as appropriate in combination with food or food ingredients. The composition according to the present invention using the active ingredient may be solid (powder, granule, etc.), paste, liquid or suspension, but can be used for the production of sweeteners, acidulants, vitamins and other drinks. It is preferable to formulate a drink for a diet or a health drink using various commonly used components.

  When used as a human and / or veterinary drug, the active ingredient is administered in various forms. Examples of the dosage form include oral administration using tablets, capsules, granules, powders, syrups and the like. These various preparations are usually used in the pharmaceutical formulation technical field such as excipients, binders, disintegrants, lubricants, flavoring agents, solubilizers, suspension agents, coating agents, etc. Can be formulated using known adjuvants. The amount to be used varies depending on symptoms, age, body weight, administration method, dosage form, etc., but usually 0.01 mg to 1000 mg per day is administered to adults per day, or in the case of intravenous administration per kg body weight. In the case of intramuscular administration, 0.01 mg to 1000 mg can also be administered. Moreover, in the case of oral administration, it is similarly 0.5-2000 mg, Preferably it is good to administer within the range of 1-1000 mg.

  Further, when used as a feed or a feed additive, it may be produced by blending an active ingredient with a commonly used feed, milk substitute, drinking water or the like in the same manner as described above. The present invention also provides a method for preventing and / or treating obesity in animals by administering an active ingredient to animals other than humans, and a method for preventing and / or treating diabetes. Accordingly, the dosage and the number of administrations may be appropriately defined, and prevention and / or treatment may be performed.

  Furthermore, the present invention was found for the first time that nucleic acid-related substances have new uses such as anti-obesity and anti-diabetes, and can be called a novel use invention. One or more of the nucleic acid-related substances are effective. By making it an ingredient, it becomes an anti-obesity, anti-diabetic food and drink, and by making it a food and drink with an indication that it is used for prevention and / or treatment of obesity, prevention and / or treatment of diabetes It is also possible to clearly distinguish from ordinary food and drink (including human and animal food and drink) containing the nucleic acid-related substance.

  Furthermore, the nucleic acid-related substance has also been newly found to have the effects of suppressing weight gain, increasing blood leptin concentration, lowering blood glucose concentration, lowering blood insulin concentration, and lowering blood NEFA concentration. Therefore, based on these new findings, a novel application invention using at least one of these actions has been completed. And in this case as well, the above-mentioned food and drink with a label indicating that one or more of the nucleic acid-related substances are used for at least one of these uses. And can be clearly distinguished.

  The present invention can control the blood glucose level by increasing the blood leptin concentration regardless of the digestive enzyme or the method of inhibiting carbohydrate absorption in the intestinal tract. At the same time, it can suppress weight gain and improve lipid metabolism, and is useful for the prevention and treatment of obesity and diabetes in humans and animals (including pets and poultry).

  Although the present invention has effects such as anti-obesity and anti-diabetes mellitus, although details of the mechanism have not been fully elucidated, suppression of weight gain, increase in blood leptin concentration, blood glucose concentration From the fact that lowering, lowering of blood insulin concentration and lowering of blood free fatty acid (NEFA) concentration are also confirmed from the examples described later, it is recognized that these actions are comprehensively involved at present. It is done.

  Thus, the mechanism of action of the present invention is very unique and characteristic, but in particular, the action of lowering blood insulin concentration by the nucleic acid-related substance is very characteristic. Since leptin is a hormone that lowers blood glucose levels and lowers appetite, it can be understood that an increase in blood leptin concentration can exert an anti-obesity effect and an anti-diabetic effect. For example, it is very characteristic in that an anti-obesity effect and an anti-diabetic effect are exhibited in spite of a decrease in blood insulin concentration.

  That is, if the insulin concentration decreases, the blood glucose level should increase. However, in the present invention, as is clear from the examples described later, the blood glucose level does not increase, but on the contrary, data that decreases completely. Is shown, and the result is completely opposite to the theory or expectation. Although the detailed mechanism must be repeated in future research, the nucleic acid-related substance does not increase the blood insulin concentration itself, but has the effect of increasing the sensitivity or sensitivity of insulin. It is presumed that the same effect as that of an increase (that is, a decrease in blood glucose level) is exhibited. This action is a conventionally unknown new action and can be used for various application developments such as the development of antidiabetic drugs.

  Moreover, since the effect show | played by this invention is achieved in the short period of only 7 days so that it may become clear also from the Example mentioned later, according to this invention, the diet food / beverage products ( Or a dieting agent). Moreover, it is also characteristic in that there is no problem with safety.

  The present invention relates to a food or drink (or agent) for preventing and / or treating obesity and / or diabetes containing as an active ingredient at least one nucleic acid-related substance selected from nucleic acid-related substances consisting of uridylic acid, uridine, and uracil. It is to provide.

  EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples. However, the present invention is not limited only to these examples.

Example 1
Twenty Wister Rat males (250 g) were used. A control group and a uridylic acid-administered group were prepared, and 10 animals were distributed per test group and a standard diet (SLC) was given. The illumination time was 12 hours.

  After a one-week acclimatization period, 44 mg / day / animal uridylic acid was dissolved in 1 ml of distilled water (13:00 daily) and fed to the uridylic acid administration group for 7 days. In the control group, physiological saline (0.9%) was similarly fed 1 ml / day / animal for 7 days, and water was freely consumed.

  Body weight was measured at the end of the pay period. Thereafter, blood was collected, plasma was separated, and blood leptin, glucose, insulin and NEFA concentrations were measured. In addition, the liver was collected and the content of neutral fat (triglyceride) was measured. The significant difference test between the control group and the uridylic acid administration group was performed by Student's t-test.

  As a result, the body weight gain during the salary period tended to decrease (FIG. 1), and the blood leptin concentration significantly increased (FIG. 2). At that time, the blood glucose concentration was significantly lowered (FIG. 3), and the insulin concentration tended to be lowered (FIG. 4). Furthermore, the blood free fatty acid (NEFA) concentration was significantly decreased (FIG. 5), and the neutral fat (TG: triglyceride) in the liver was significantly decreased (FIG. 6).

  From the above, it was demonstrated that uridylic acid has an effect of suppressing body weight gain and promoting leptin secretion. At that time, the blood glucose / insulin concentration was also kept low in the normal range, became high during diabetes, and the blood NEFA concentration and liver TG concentration that worsen the insulin resistance of each tissue decreased. From these, it was shown that it can be applied to the prevention and treatment of obesity and diabetes.

The amount of weight gain from the end of the habituation period to the end of the salary period (one week) is shown. The leptin concentration in the blood collected after the end of the feeding period is shown. It shows the glucose concentration in blood collected after the end of the feeding period. The insulin concentration in the blood collected after the end of the feeding period is shown. The NEFA concentration in blood collected after the end of the feeding period is shown. The TG concentration per gram of liver collected after the end of the feeding period is shown.

Claims (1)

A human diabetes preventive and / or therapeutic agent characterized by comprising only uridylic acid as an active ingredient, increasing blood leptin concentration, and decreasing blood glucose concentration and blood insulin concentration.

Images