JP2012158553A - Visceral fat accumulation inhibitor - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a visceral fat accumulation inhibitor having high safety and an excellent anti-obesity effect.SOLUTION: A culture fermented product by a Monascus purpureus is used as an active ingredient of a visceral fat accumulation inhibitor.

Description

The present invention relates to a visceral fat accumulation inhibitor having a high safety and an excellent anti-obesity effect since it is derived from natural products and has abundant dietary experience. Moreover, this invention relates to the pharmaceutical containing the said fat accumulation inhibitor.

  Visceral fat-type obesity is a major component of the metabolic syndrome that often involves diabetes, hypertension, hyperlipidemia, etc., and develops arteriosclerosis such as stroke and myocardial infarction. When obesity worsens, the pathological conditions of the above-mentioned diseases further worsen, so obesity is a typical lifestyle-related disease, and is considered to be located more upstream in the metabolic syndrome.

  Until now, insulin resistance has been attracting attention as the core of the metabolic syndrome, but in recent years, various hormones and cytokines produced and secreted by fat cells have been associated with the pathogenesis of obesity and lifestyle-related diseases. It has become clear that it is involved in formation. For example, of the hormones secreted by adipocytes, adiponectin is a hormone that is present in large amounts in the blood and is involved in the body's defense mechanisms such as anti-inflammatory and arteriosclerosis repair, but when visceral fat increases, Adiponectin concentration is known to decrease. In other words, it is considered to be a hormone that plays an important role in preventing and improving obesity. Leptin also suppresses feeding and increases energy metabolism, and its lack of action is thought to play an important role in the pathogenesis of obesity. Increases in proportion to body fat mass. That is, it is generally considered that obese people are in a state of insufficient action due to leptin resistance.

  Furthermore, when fat accumulates in the liver (fatty liver), hepatocytes break (hepatitis), resulting in cirrhosis to liver cancer. In recent years, the number of patients with non-alcoholic fatty liver disease caused by such obesity is increasing. According to statistics from the Ministry of Health, Labor and Welfare, one in every two men aged 40 to 74 and one in every five women are said to be eligible for metabolic syndrome Together with an estimated 20.1 million people. Moreover, it is said that if all the symptoms such as hyperglycemia, dyslipidemia, and hypertension overlap, it is 30 times more dangerous than a person who does not have any of the symptoms.

  Accordingly, there is a need for an obesity inhibitor that can be safely ingested on a daily basis, which suppresses and improves the accumulation of visceral fat that forms the basis of metabolic syndrome.

  By the way, red yeast rice is a rice cake made by breeding Monascus strains on cereals and has been used as a raw material for brewing red wine, old sake, and red milk tofu in China, Taiwan, etc. It is a highly safe material with abundant dietary experience, as is known for its effects such as "spleen dry stomach". Conventionally, it has been clarified that red yeast rice has pharmacological actions such as blood pressure lowering action and cholesterol improving action.

  For example, Patent Document 1 discloses an antihypertensive agent comprising, as an active ingredient, cocoons produced using filamentous fungi belonging to the genus Monascus. However, Patent Document 1 does not disclose whether or not red yeast rice has an effect of suppressing fat accumulation. Patent Document 2 discloses that red yeast rice produced using soybeans, wheat or malt as a koji raw material together with white rice contains a blood pressure lowering component. However, Patent Document 2 also does not report on the presence / absence of the suppression effect of red yeast rice on fat accumulation. Furthermore, Patent Document 3 discloses that the koji obtained by culturing fungi belonging to the genus Monascus has a cholesterol lowering action and a blood sugar lowering action. Not disclosed.

JP-A 61-197524 JP 2000-279163 A JP-A-57-146570

  Therefore, an object of the present invention is to provide a visceral fat accumulation inhibitor having high safety and an excellent fat accumulation inhibitory effect. Moreover, an object of this invention is to provide the pharmaceutical containing the said fat accumulation inhibitor.

  As a result of intensive studies to solve the above-mentioned problems, the present inventors have found that a cultured fermented product of Monascus has an excellent fat accumulation suppressing effect. The present invention has been completed by making further improvements based on this finding.

That is, the present invention provides the following inventions:
Item 1. A visceral fat accumulation inhibitor containing, as an active ingredient, a cultured fermented product of Monascus.
Item 2. Item 2. The visceral fat accumulation inhibitor according to Item 1, wherein the fermented product is rice red koji.
Item 3. Item 3. The visceral fat accumulation inhibitor according to Item 1 or 2, which is an adiponectin production promoter.
Item 4. Item 3. The visceral fat accumulation inhibitor according to Item 1 or 2, which is a leptin production inhibitor.
Item 5. Item 3. The visceral fat accumulation inhibitor according to Item 1 or 2, which is an insulin resistance improving agent.
Item 6. Item 3. The visceral fat accumulation inhibitor according to Item 1 or 2, which is a fatty liver alleviator.
Item 7. Item 3. The visceral fat accumulation inhibitor according to Item 1 or 2, which is a liver function improving agent.
Item 8. Item 8. A pharmaceutical comprising the visceral fat accumulation inhibitor according to any one of Items 1 to 7.

  The visceral fat accumulation inhibitor of the present invention, in addition to the effect of suppressing increase or enlargement of visceral fat, the effect of increasing or reducing the amount of adiponectin production, the effect of reducing or increasing the amount of leptin production The effect of improving insulin resistance, and the effect of alleviating fatty liver or improving liver function are exhibited.

It is the figure which showed the amount of adiponectin in Table 1. It is the figure which showed the amount of leptin in Table 1. It is the figure which showed the amount of insulin in Table 1. It is the figure which showed the testicular fat amount in Table 2.

  The present invention is described in detail below. The visceral fat accumulation inhibitor of the present invention is characterized by comprising a cultured fermented product of Aspergillus niger as an active ingredient.

  The cultured fermented product of koji mold which is an active ingredient of the visceral fat accumulation inhibitor of the present invention is obtained by koji making koji raw material using koji mold.

  As the raw material for koji, any raw material can be used as long as it can be used for the preparation of koji. For example, various types of grains such as polished rice, brown rice, wheat, koji, mulberry, buckwheat, corn, soybeans, red beans, Spider, bran, embryo, rice bran, etc. can be used. Preferably, it is polished rice. Further, it may be shaped like crushed rice, and the place of origin and variety are not particularly limited. These raw materials may be used alone or in combination of two or more. Furthermore, various ingredients necessary for the propagation of red koji molds, for example, a carbon source, a nitrogen source, inorganic substances, vitamins, and the like may be added to these raw materials as necessary.

  The koji raw material is preferably sterilized by known means such as heating and pressure heating prior to koji making.

In the present invention, the koji mold used in preparing the cultured fermented product can be used without particular limitation as long as it is food hygiene or pharmaceutically acceptable. As the red koji mold, specifically, a filamentous fungus belonging to the genus Monascus , more specifically, Monascus purpureus , Monascus anka , Monascus ruber ( Monascus ruber ) Monascus pilosus , these variants, and mutants thereof. In particular, Monascus pilosus , which has a track record as an edible product and has excellent flavor and appearance, is preferably used. These red koji molds may be used singly or in combination of two or more.

  In the present invention, the koji making using the koji mold is carried out by inoculating the koji mold on the koji raw material and mixing well, followed by culturing under aerobic conditions.

  The temperature condition at the time of koji making is not particularly limited as long as the above koji mold can grow, but is usually 20 to 37 ° C, preferably 25 to 35 ° C.

  The pH of the medium is 4.0 to 8.0, preferably 4.5 to 7.0 during the culture period. In addition, the time required for the koji making varies depending on the type of koji mold used, the type of koji making material used, etc., and cannot be uniformly defined, but is usually 5 to 20 days, preferably 7 to 14 days. is there.

  During the ironmaking period, water or a pH adjusting agent can be added once or several times during the ironmaking period to adjust the water content or pH to be maintained in the above range.

  The culture fermented product obtained from the koji mold thus obtained contains a substance having an excellent visceral fat accumulation-inhibiting effect, and the cultured fermented product is not only used as it is, but also all known methods for using koji. It can be used in the form of For example, those that have been processed by a conventional method such as inactivated bacteria and enzymes, dried products, dried pulverized products, powders, granules, aqueous solutions, pastes, extracts, extract extracts concentrates, extract extracts, etc. It can be used as an active ingredient of a visceral fat accumulation inhibitor.

  Moreover, as the visceral fat accumulation inhibitor of the present invention, an extract of the cultured fermented product can be used in addition to the cultured fermented product.

  The extract of the cultured fermented product can be obtained by extracting a water-soluble fraction from the cultured fermented product using an extraction solvent. Specifically, the extract of the cultured fermented product can be obtained by extracting the cultured fermented product as it is or after subjecting the fermented fermented product to processing such as shredding or crushing with an extraction solvent. Examples of the extraction solvent include water such as cold water, warm water and hot water; organic solvents; or a mixture of water and organic solvents. Examples of the organic solvent used as the extraction solvent include lower alcohols such as methanol, ethanol, propanol, isopropanol, and butanol. Preferred examples of the extraction solvent include water and a mixed solution of water and ethanol. When using a mixed solution of water and an organic solvent as the extraction solvent, the content ratio of the organic solvent to the total weight of the mixed solution is, for example, 1 to 99% by weight, preferably 1 to 50% by weight. Can be mentioned.

  The visceral fat accumulation-suppressing agent of the present invention suppresses increase or enlargement of visceral fat based on its fat accumulation-inhibiting action, and is useful for the prevention or treatment of obesity. In particular, adiponectin, which is known to play an important role in the prevention and improvement of obesity, can increase the blood concentration, and lack of action is thought to play an important role in the pathogenesis of obesity The blood concentration of leptin can be reduced. Insulin resistance involved in obesity can also be improved. Furthermore, fat accumulation in the liver can be suppressed, fatty liver can be relieved, and liver function can be improved.

  The visceral fat accumulation inhibitor of the present invention is used in the field of pharmaceuticals, thereby providing a pharmaceutical for obesity suppression. In view of the fact that the visceral fat accumulation inhibitor of the present invention is composed of food components and is safe even if taken daily, it can be applied to food additives and foods.

  Moreover, in the pharmaceutical field, the visceral fat accumulation inhibitor of the present invention is formulated with a pharmaceutically acceptable base material and carrier, and is prepared and used as a pharmaceutical product for inhibiting obesity. The medicine may optionally contain pharmaceutically acceptable additives such as a binder, a disintegrant, a lubricant, a wetting agent, a buffer, a preservative, and a fragrance. Although it does not restrict | limit especially as a form of the said pharmaceutical assembly, For example, a powder, a tablet, a granule, a capsule, a syrup agent etc. can be mentioned.

  The dose of a pharmaceutical containing a visceral fat accumulation inhibitor varies depending on the type of active ingredient, the age and weight of the administration subject, symptoms, the number of administrations, etc., and cannot be specified uniformly. Examples of the dose include an amount corresponding to 1 to 100 g of the visceral fat accumulation inhibitor in terms of the dry weight of the cultured fermentation product.

  About the administration frequency of the pharmaceutical containing a visceral fat accumulation inhibitor, it can set suitably according to the kind of active ingredient, the age and weight of a subject, the symptom, the dosage per time of this pharmaceutical, etc.

  In addition, what is necessary is just to set suitably about the compounding ratio of this fat accumulation inhibitor in the pharmaceutical containing a visceral fat accumulation inhibitor according to the form of the said pharmaceutical, the said dosage, etc.

  EXAMPLES Hereinafter, although an Example is given and this invention is demonstrated, this invention is not limited to these Examples.

Example Polished rice was immersed in water for 90 minutes, drained for 45 minutes, and then autoclaved at 125 ° C. for 30 minutes in an autoclave.
Next, Monascus pilosus NBRC4520 was inoculated into this koji raw material, and cultured at a temperature of 25 to 30 ° C. for 10 days to obtain rice red koji.
The rice red koji obtained above is heat-treated at 110 ° C. for 30 minutes, the red koji mold and the enzyme are deactivated, dried at 60 ° C. to a moisture content of about 10%, and pulverized to obtain a red koji powder. It was.

Test example 1
<Evaluation of efficacy of red yeast rice for MSG obesity model mice>
The red yeast rice powder obtained in the examples was added to the standard diet at a ratio of 1% by weight, and given to the following MSG obese model mice (12-week-old male) for 3 months up to the age of 24 weeks. Control group mice received a standard diet only.
Table 1 shows the results of blood tests 3 months after administration and organ tests after dissection. As a result, it has been clarified that it is effective for adipocyte improvement, adiponectin increase, leptin decrease, insulin resistance improvement, and fatty liver improvement.

(MSG mouse; experimental diabetes model)
It is a severe obesity model that can be induced by administering sodium glutamate to newborn mice, and a model that develops non-alcoholic liver disease. As obesity progresses, type 2 diabetes develops, and in addition to hyperglycemia, high insulin, impaired glucose tolerance, abnormalities in total cholesterol, neutral fat, and the like are also confirmed.

非アルコール性脂肪性肝疾患活性スコア：
非アルコール性脂肪性肝疾患の程度の指標であり、肝細胞の脂肪変性、肝小葉の炎症、肝細胞肥大、線維化を複合的に評価した数値

Nonalcoholic fatty liver disease activity score:
It is an index of the degree of non-alcoholic fatty liver disease and is a composite evaluation of hepatocyte steatosis, hepatic lobule inflammation, hepatocyte hypertrophy, and fibrosis

Test example 2
<Efficacy evaluation of red yeast rice for TSOD obesity model mice>
The red yeast rice powder obtained in the Examples was added to the standard diet at a ratio of 3% by weight, and given to the following TSOD mice (8-week-old male) for 3 months up to the age of 20 weeks. Control group mice received a standard diet only.
Table 2 shows the results of blood tests 3 months after administration and organ tests after dissection. As a result, it became clear that it was effective for improvement of adipocytes, reduction of leptin, improvement of insulin resistance, blood glucose level, neutral fat and free fatty acid.

(TSOD mouse; genetic diabetes model)
Spontaneous visceral fat-accumulating obese mice with confirmed pathological conditions such as increased visceral fat, decreased glucose tolerance, decreased insulin sensitivity, kidney damage, peripheral neuropathy, osteoporosis, lipid metabolism disorder, male reproductive dysfunction It exhibits symptoms similar to those caused by human obesity and diabetes.

Claims (8)

A visceral fat accumulation inhibitor containing, as an active ingredient, a cultured fermented product of Monascus. The visceral fat accumulation inhibitor according to claim 1, wherein the fermented product is rice red yeast rice. The visceral fat accumulation inhibitor according to claim 1 or 2, which is an adiponectin production promoter. The visceral fat accumulation inhibitor according to claim 1 or 2, which is a leptin production inhibitor. The visceral fat accumulation inhibitor according to claim 1 or 2, which is an insulin resistance improving agent. The visceral fat accumulation inhibitor according to claim 1, which is a fatty liver alleviator. The visceral fat accumulation inhibitor according to claim 1 or 2, which is an agent for improving liver function. A pharmaceutical comprising the visceral fat accumulation inhibitor according to any one of claims 1 to 7.

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