JP2008074794A - Obesity preventive or ameliorating agent - Google Patents

Abstract

Disclosed is a pharmaceutical product or food having an excellent lipid accumulation-inhibiting action, excellent in safety, and effective in preventing or improving body fat accumulation, obesity, fatty liver, and various diseases caused by or related to these. Etc offer.
An agent for preventing or improving obesity comprising lysophospholipid as an active ingredient.
[Selection figure] None

Description

  The present invention relates to an agent for preventing or improving obesity and fatty liver.

  In recent years, obesity has become a social problem due to changes in dietary habits and lack of exercise. Obesity is a type of lifestyle-related disease called death quartet together with hypertension, hyperlipidemia and diabetes, and is known to be a risk factor for further diseases such as arteriosclerosis. In addition, the condition in which fat accumulates in the liver is called fatty liver, but the number of patients continues to increase. At present, it is estimated that about 20% of Japanese people have fatty liver ( Survey report of Ikaihara Medical Center, Tokai University School of Medicine). It is known that fatty liver not only contributes to the onset and worsening of lifestyle-related diseases, but also causes liver disorders such as hepatitis and cirrhosis (Non-patent Document 1). Thus, it is important to prevent obesity and fatty liver in order to prevent lifestyle-related diseases and liver damage.

  In general, obesity is a state in which neutral fat accumulates as a result of maintaining a state of excessive intake energy as compared with consumed energy, resulting in a significant increase in body weight. Therefore, preventing or treating obesity by reducing the intake energy is an effective means. As drugs that reduce the intake energy, central appetite suppressants such as mazindol (Non-patent Document 2) and sibutramine (Non-patent Document 3) and pancreatic lipase inhibitors such as orlistat (Non-patent Document 4) are known. However, side effects such as dry mouth, constipation and stomach discomfort may occur with central appetite suppressants, while side effects in the digestive tract such as diarrhea and fatty stool may occur with orlistat. Is desired.

  In addition, fatty liver is a state in which excess neutral fat is accumulated in the liver. Therefore, it is an effective means to prevent or treat fatty liver by suppressing synthesis of neutral fat in the liver. A nicotinic acid preparation is a drug that suppresses liver triglyceride synthesis, but it has impaired liver function as a side effect and is not suitable for the treatment of fatty liver. In addition, as a food ingredient, there is reported a liver neutral fat synthesis inhibitory action on vegetable proteins such as soybean protein and docosahexaenoic acid contained in a large amount in fish oil (Non-patent Documents 5 and 6). These food ingredients are not fully satisfactory in their effectiveness. Therefore, there is a need for food materials that are highly effective, have abundant food experience, and are highly safe.

On the other hand, lysophospholipid is widely used as a stable emulsifier with high hydrophilicity, and itself has a fatigue-reducing action by supplying choline (Patent Document 1). It has been reported (Patent Document 2).
However, nothing is known about the relationship between lysophospholipids and obesity or fatty liver.
JP 62-1111920 A JP 2001-31551 A Ludwig, J., Mayo Clin Proc. 55, 434-438 (1980) Engsrom, RG, Arch.Intern.Pharmacodyn. 214,308-321 (1975) Bray, GA, Obes.Res. 4, 263-270 (1996) Davidson, MH, J. Ame. Med. Asso. 281,235-242 (1999) Ascencio, C., J. Nutr., 134, 522-529 (2004) Kim, HJJBiol. Chem. 274, 25892-25898 (1999)

  The present invention relates to providing a pharmaceutical or a food that is excellent in safety and effective in preventing or ameliorating obesity, fatty liver, and various diseases caused or caused by these.

  As a result of searching for various natural ingredients, the present inventors have found that lysophospholipids suppress the accumulation of liver lipids and exert an effect of inhibiting fatty liver, and reduce visceral fat and exhibit an anti-obesity effect. It was.

That is, the present invention relates to the following inventions.
1) An obesity preventive or ameliorating agent comprising lysophospholipid as an active ingredient.
2) A preventive or ameliorating agent for fatty liver containing lysophospholipid as an effective component.
3) Use of lysophospholipid for the manufacture of an agent for preventing or improving obesity.
4) Use of lysophospholipid for the manufacture of an agent for preventing or improving fatty liver.
5) A food containing lysophospholipid as an active ingredient and having an effect of preventing or ameliorating obesity or fatty liver, and labeled accordingly.

  The obesity prevention or amelioration agent and fatty liver prevention or amelioration agent of the present invention exhibit excellent anti-obesity effect, liver lipid accumulation suppression effect, and high safety. Or it is useful as a pharmaceutical or a food for preventing or ameliorating various diseases that develop in relation, for example, diabetes, hypertension, hyperlipidemia, arteriosclerosis.

The lysophospholipid is a lyso form in which either one of the α-position or β-position fatty acid residue of glycerophospholipid is removed by hydrolysis. Specifically, lysophosphatidylcholine, lysophosphatidylethanolamine, lysophosphatidylinositol, lysophosphatidine An acid etc. are mentioned.
Lysophospholipids are obtained by treating phospholipids with an enzyme such as phospholipase A _{2. In} the present invention, phospholipids for obtaining lysophospholipids include animals and plants such as soybeans, rice, corn, rapeseed, cotton. A process for producing extracted lecithin extracted from animal tissues such as fruit, wheat, peanut, sunflower, sunflower, barley, oat, safflower, sesame, etc., egg yolk, milk, seafood, etc., preferably soybean oil It is preferable to use an insoluble fraction obtained by treating the crude lecithin generated in step 1 with acetone, ethanol or the like. Further, purified lecithin obtained by purifying crude lecithin may be used. Alternatively, phospholipids such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidic acid may be treated with an enzyme. In this case, the lysophospholipid may be used singly or in combination, or Can be used in combination. Moreover, you may use commercial items, such as SLP-white lyso (Tsubaki Oil).

As will be described later in Examples, lysophospholipid has an action to suppress accumulation of liver lipid and an anti-obesity action. Therefore, the lysophospholipid can be used as an agent for preventing or improving fatty liver and obesity, and can be used for producing an agent for preventing or improving fatty liver and obesity.
Such an agent for preventing or improving fatty liver, an agent for preventing or improving obesity is obesity, fatty liver, and various diseases caused by or associated with them, such as diabetes, hypertension, hyperlipidemia, arteriosclerosis. It can be used as a human or veterinary drug, quasi drug or food for prevention or improvement.
Fatty liver preventive or ameliorating agent, obesity preventive or ameliorating agent is based on the concept of preventing or improving fatty liver or obesity, and if necessary, beauty food, food for the sick or food for specified health use, etc. It can be used as a functional food.

  Examples of the administration form when the agent for preventing or improving fatty liver or the agent for preventing or improving obesity of the present invention is used as a pharmaceutical include, for example, tablets, capsules, granules, powders, syrups, enteric solvents, troches, drinks, etc. Oral administration or parenteral administration by injection, suppository, percutaneous absorption agent, external preparation and the like can be mentioned. In order to prepare pharmaceutical preparations of such various dosage forms, the lysophospholipid of the present invention alone or other pharmaceutically acceptable excipients (sorbitol, glucose, lactose, dextrin, starch, etc.) Saccharides, inorganic substances such as calcium carbonate, crystalline cellulose, distilled water, sesame oil, corn oil, olive oil, rapeseed oil, etc.), binders, lubricants, extenders, disintegrants, surfactants, lubricants, dispersants, Suspending agents, emulsifiers, buffers, preservatives, flavoring agents, fragrances, coating agents, carriers, diluents, antioxidants, bacterial inhibitors, and the like can be used in appropriate combinations. Among these dosage forms, the preferred form is oral administration, and when used as a preparation for oral administration, the content of the lysophospholipid of the present invention in the preparation is generally 0.01 to 95% by mass. Is preferable, and it is more preferable to set it as 10-80 mass%.

Examples of the form in the case of using the fatty liver preventing or improving agent, obesity preventing or improving agent of the present invention as foods include, for example, processed foods such as bread, noodles and the like, processed rice foods such as rice cakes and cooked rice Biscuits, cakes, jelly, chocolate, rice crackers, ice cream and other sweets, tofu, processed foods such as processed foods, soft drinks, fruit juices, milk drinks, carbonated drinks, yogurt, cheese, butter, For dairy products such as milk, seasonings such as soy sauce, sauce, miso, mayonnaise, dressing, meat storage such as ham, bacon, sausage, meat storage processed foods, marine processed foods such as hampen, chikuwa, canned fish, cooking oil and frying Oil etc. are mentioned. In addition, it may be in the form of tablet foods such as capsules, concentrated liquid foods, natural liquid foods, semi-digested nutritional foods, component nutritional foods, drink nutritional foods, oral enteral nutrition foods, functional foods, etc. it can.
To prepare various forms of food, the lysophospholipid of the present invention alone or other food materials, solvents, softeners, oils, emulsifiers, preservatives, fragrances, stabilizers, colorants, antioxidants An agent, a humectant, a thickener and the like can be used in appropriate combination. In general, the content of the lysophospholipid of the present invention in the food is preferably 0.01 to 20% by mass, and more preferably 0.1 to 10% by mass.

  When the agent for preventing or improving fatty liver or the agent for preventing or improving obesity of the present invention is used as a medicine or food, the daily administration or intake per adult is 50 to 10,000 mg as the lysophospholipid of the present invention, for example. Of 100 to 6000 mg, more preferably 500 to 3000 mg. The preparation is preferably administered once to several times a day.

Example 1 Inhibitory Effect of Lysophospholipid on Accumulation of Liver Lipid Experimental animals were male BKS. Cg− + Lepr ^db / + Lepr ^db / Jcl mice (db / db, 6 weeks old) were preliminarily raised on a commercial chow for 1 week, and then divided into 2 groups (6 animals per group) so that the average body weight was equal. Used for experiments.
Triacylglycerol oil used for the test was a mixed oil of rapeseed oil, safflower oil and refined sesame oil. The fatty acid composition contained C16: 0 5.6%, C18: 0 2.1%, C18: 1 36.7%, C18: 2 46.9%, C18: 3 6.8%. As the lysophospholipid, lysophospholipid (SLP-white lyso) purchased from Sumi Oil was used. SLP-white lyso used for the test contains 18% to 30% of lysophospholipid as a phospholipid composition.
The control group was fed with a diet containing 10 g triacylglycerol oil, 13 g sucrose, 20 g casein, 4 g cellulose powder, 3.5 g mineral mixture, 1 g vitamin mixture, 48.5 g potato starch per 100 g. The test group was fed with a diet in which 3 g of triacylglycerol oil was replaced with lysophospholipid from the above diet, and was bred for 1 month. During the test period, the test food and water were freely consumed. There were no differences between groups in the intake of test food and water during the study period.

  After one month of breeding, the mouse was laparotomized under ether anesthesia, blood was collected from the abdominal vena cava, and the liver was removed. Liver lipids were extracted from a part of the extracted liver according to the method of Folch et al. (Folch, J., J. Bio. Chem., 23, 497-509 (1957)). The extracted liver lipid was measured using triglyceride E-test Wako (GPO / HDAOS method, glycerin elimination method) and the amount of liver triacylglycerol accumulated using total cholesterol E-test Wako (GPO / DAOS method).

  As shown in FIG. 1, the amount of hepatic triacylglycerol accumulated was significantly reduced by ingestion of lysophospholipid. Similar to triacylglycerol, intake of lysophospholipid significantly decreased the total amount of accumulated liver cholesterol (FIG. 2). From this, it can be seen that lysophospholipid suppresses accumulation of lipids in the liver and is effective in suppressing fatty liver.

Example 2 Anti-obesity effect of lysophospholipid Experimental animals were male BKS. Cg− + Lepr ^db / + Lepr ^db / Jcl mice (db / db, 6 weeks old) were preliminarily raised on a commercial chow for 1 week, and then divided into 2 groups (6 animals per group) so that the average body weight was equal. Used for experiments.
In the same manner as in Example 1, a control group and a test food group were provided and reared for one month. During the test period, the test food and water were freely consumed. There were no differences between groups in the intake of test food and water during the study period. After one month of breeding, the body weight was measured.

  As shown in Table 1, the body weight after the test period was significantly reduced by ingestion of lysophospholipid. This shows that lysophospholipid has an anti-obesity effect.

Example 3
SLP-white lyso (Tsubaki Oil) was filled into a gelatin capsule to obtain a soft capsule of 300 mg per tablet.

Example 4
Using the following ingredients, one tablet of 300 mg was produced according to a conventional method.
Composition (mg); SLP-white lyso (smoked oil) 100, hydroxypropylcellulose 60, light anhydrous silicic acid 10, lactose 35, crystalline cellulose 35, talc 30, diacylglycerol 30

Example 5
Using the following ingredients, one tablet of 300 mg was produced according to a conventional method.
Composition (mg); SLP-white lyso (boiled oil) 100, starch 150, magnesium stearate 10, lactose 40

Example 6 Chocolate for Fatty Liver Inhibition / Obesity Inhibition Commercially available 100 g of black chocolate was dissolved at 60 ° C. for 1 hour. A lysophospholipid-containing chocolate was obtained by adding 2% by weight of SLP-white lyso (boiled oil) to this and tempering.

Example 7 Pan for Fatty Liver Inhibition / Obesity Inhibition After mixing the following ingredients, the raw material was fermented, then squeezed, subjected to shaping and roasting to obtain a phospholipid-containing bread.
Composition (g): SLP-white lyso 1.0, strong powder 100, yeast 2, salt 2, sugar 3, shortening 3, yeast food 0.15, water 60

Example 8 Fatty liver suppression / obesity suppression cream A raw material mixed with the following components was heated to 80 ° C., homogenized at 60 kg / cm ² using a homogenizer, and held in a refrigerator at 5 ° C. for 12 hours. After maintaining at 5 ° C. for 12 hours, the mixture was whipped at 400 rpm for 4 minutes using a whipping stirrer to obtain a phospholipid-containing whipped cream.
Composition (g): SLP-white lyso 0.5, water 43.35, vegetable oil and fat 30 of melting point 30 ° C., skim milk 25, sucrose fatty acid ester 0.4, monoglyceride 0.1, tripotassium phosphate 0.15

Example 9 Fatty liver suppression / obesity suppression coffee The raw material mixed with the following ingredients was heated to 80 ° C., homogenized at 150 kg / cm ² using a homogenizer, and 250 ml in a 250 ml stainless steel can was filled. Covered with a cinching machine. This was sterilized at 120 ° C. for 10 minutes in a retort kettle and then cooled to 10 ° C. to obtain a phospholipid-containing coffee.
Composition (g): SLP-white lyso 0.2, water 40, milk 8, sugar 10, instant coffee powder 2, monoglyceride 0.1

The graph which shows the change of the liver triacylglycerol accumulation amount by lysophospholipid intake. The graph which shows the change of the liver total cholesterol accumulation amount by lysophospholipid intake.

Claims (5)

  An agent for preventing or improving obesity comprising lysophospholipid as an active ingredient.   An agent for preventing or improving fatty liver, comprising lysophospholipid as an effective component.   Use of lysophospholipid for the manufacture of an agent for preventing or improving obesity.   Use of lysophospholipid for the manufacture of an agent for preventing or improving fatty liver.   A food containing lysophospholipid as an active ingredient and having an effect of preventing or improving obesity or fatty liver, and a label to that effect.

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