JP2011057599A - Energy metabolism-promoting agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To pay an attention on sterol glycosides contained in germinated unpolished rice to clarify a new action mechanism thereof. <P>SOLUTION: There are provided an energy metabolism-promoting agent containing sterol glycosides originated from germinated unpolished rice as an active ingredient, and a food or drink (excluding germinated unpolished rice) containing the energy metabolism-promoting agent. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to an energy metabolism enhancer.

It is important to prevent obesity so as to be a source of all illness. In particular, as one of obesity, metabolic syndrome (visceral fat syndrome) has recently attracted attention as an indicator of health damage. Metabolic syndrome (visceral fat syndrome) refers to a condition in which at least two of hyperglycemia, hypertension, and lipid abnormalities are combined in addition to visceral fat obesity. When visceral fat accumulates excessively, lifestyle-related diseases such as diabetes, hypertension, and hyperlipidemia are likely to occur. Moreover, arteriosclerosis rapidly progresses by the simultaneous occurrence of the spare groups that have not yet been diagnosed with illness, such as “a little higher blood sugar level” and “a little higher blood pressure”.
As food becomes richer during the high economic growth period, infections and strokes decrease, but conversely, the rate of obesity, hypertension, dyslipidemia, and diabetes increases dramatically, resulting in myocardial infarction and cerebral infarction caused by these diseases. Serious cardiovascular diseases such as have changed to the structure that accounts for the top causes of death. In particular, cardiovascular diseases triggered by visceral fat accumulation-type obesity develop in the working generation, and in the worst case, they may die, and even if they can save their lives, they cause severe disability and make life difficult. You may be forced to be free. Amid the declining birthrate and aging population, causing a crisis in the lives of active generations is seen as a major loss for society, and there is a need for an effective means of preventing chronic diseases that develop from metabolic disorders. Researchers in various fields of medicine, nutrition, and agriculture have been working on solving the problem, but no effective means to solve multiple metabolic disorders has been found. Diabetes causes a variety of diseases. Measures are taken to control and control an increase in blood glucose level as a countermeasure and prevention of diabetes.
In addition, lack of exercise is a major factor in abnormal energy metabolism as well as overeating. On the other hand, habitual exercise increases insulin sensitivity and has various positive effects on blood sugar and lipid profiles. Exercise directly improves diabetes and hyperlipidemia by promoting glucose uptake and fatty acid burning in skeletal muscle. It is also a well-known exercise utility to improve insulin resistance by eliminating the lipotoxicity associated with obesity (particularly visceral obesity).

The present applicant, the present inventors, etc. have continued research and development focusing on germinated brown rice, and have made many proposals such as the development of germinated brown rice itself and inventions relating to the functions of the components contained in germinated brown rice. . As a proposal focusing on functional components, for example, Patent Document 1 (Japanese Patent Application Laid-Open No. 2008-266326) proposes a preventive or ameliorating agent for neuropathy or diabetic neuropathy comprising a germinated brown rice total lipid fraction as an active ingredient. Yes. Patent Document 2 (Japanese Patent Laid-Open No. 2006-316018) proposes a glucocorticoid receptor antagonist and an adrenergic β3 receptor agonist containing allylatose B extracted from sprouted brown rice bran. Patent Document 3 (Japanese Patent Application Laid-Open No. 2006-31616) proposes an insulin receptor agonist containing lysophosphatidylcholine having a specific chemical structure extracted from sprouted brown rice bran.
Japanese Patent Application Laid-Open No. 2006-223224, Japanese Patent Application Laid-Open No. 2007-161638, and Japanese Patent Application Laid-Open No. 2004-149494 have been proposed for improving energy metabolism.

JP 2008-266326 A JP 2006-316018 A JP 2006-31016 A JP 2006-223224 A JP 2007-161638 A JP 2004-149494 A

  This inventor pays attention to the sterol glycoside fraction contained in germinated brown rice, and makes it the subject of this invention to clarify the new action mechanism. In particular, it is an object to clarify the energy metabolism enhancing action.

That is, the main configuration of the present invention is as follows.
1. An energy metabolism enhancer comprising a sterol glycoside derived from germinated brown rice bran as an active ingredient.
2. 1. Food / beverage products (except germinating brown rice) containing the energy metabolism enhancer described in 1.
3. 1. Pet food containing energy metabolism enhancement as described in (except germinating brown rice).

  The present invention has revealed that sterol glycosides derived from germinated brown rice have an energy metabolism enhancing action. By ingesting this germinated brown rice-derived sterol glycoside in the form of medicine, food and drink, etc., energy metabolism can be enhanced. This can also be used for pets. Since it is derived from germinated brown rice, it is highly safe and exerts an energy metabolism enhancing effect with a very small intake.

Breath analysis (oxygen consumption) Spontaneous momentum comparison graph

The sterol glycoside fraction extracted from germinated brown rice used in the present invention (hereinafter sometimes referred to as “ASG”) is obtained by removing neutral lipids from cocoon obtained from germinated brown rice with hexane, and the resulting residue Is further contained in a lipid fraction extracted with an organic solvent, and can be separated and concentrated by high performance liquid chromatography (HPLC).
The present invention is an energy metabolism enhancer comprising as an active ingredient a sterol glycoside derived from germinated brown rice. The ingestion method can be performed orally or by injection, and can be used as an additive for pharmaceuticals, foods and drinks, food additives, pet pharmaceuticals, and pet feeds. Since it is a component derived from germinated brown rice that is usually used for food, it is highly safe.
Since ASG is a component that is extracted in a trace amount from the rice bran component of germinated brown rice, when ASG is applied to medicine or food and drink, pet medicine and feed, the extracted ASG itself is used. It is not assumed to be used in a state before extracting ASG such as brown rice itself or germinated brown rice powder.

The present invention can be used as an energy metabolism enhancer, food additive, food and pet food, animal medicine. The dosage form can be formulated into an arbitrary form together with an auxiliary agent by a known method and taken orally (administered). It can be ingested (administered) as a capsule or tablet, granule, fine granule, powder, or liquid.
Ingestion (administration) amount may vary depending on the ingestion (administration) method and the subject's age, medical condition, general condition, etc. From the results of animal studies, in adults, it is usually 0.4 to 600 mg as an active ingredient per day for 1 kg body weight. Is appropriate.

The energy metabolism-enhancing agent of the present invention can be added to general foods and health foods, and can also be used as a component of food additives. The food to be blended is not particularly limited, for example, bakery foods such as bread, confectionery bread, pies, Danish, donuts, cakes, noodles such as udon, soba, Chinese noodles, yakisoba, pasta, fries such as tempura, croquettes, curry, Sources such as stew and dressing, sprinkles, kneaded products such as kamaboko, beverages such as juice, snacks, rice confectionery, rice cake, confectionery such as gum.
Suitable for pets as feed for mammals such as dogs, cats, hamsters and squirrels. The form of the pet food of the present invention is not particularly limited, and examples thereof include dry type, wet type, semi-moist type, biscuit type, sausage type, jerky type, powder, granule, capsule and the like.

<Sterol glycoside derived from germinated brown rice>
1. Germinated brown rice from which the koji component is collected can be prepared by a known method. The present applicant has made a number of proposals for germinated brown rice, which can be obtained, for example, by the method for producing germinated brown rice disclosed in Japanese Patent No. 3423927, Japanese Patent No. 3611804, Japanese Patent No. 3738025, and the like.
The germinated brown rice is refined by about 5 to 15% and the koji component is collected. The soot component is first degreased with hexane. This degreasing step is the same as the method for collecting rice bran oil by degreasing general rice bran. In the present invention, the sterol glycoside fraction is further extracted using the defatted koji as a raw material and further using an organic solvent.

2. The present applicant has previously proposed, as Japanese Patent Application No. 2008-56730, a sterol glycoside represented by the formula (1) extracted from germinated brown rice. The ASG used in the present invention has been found to contain this sterol glycoside. This sterol glycoside is abbreviated as ASG. It was clarified that this ASG has an effect of preventing and improving neuropathy.

(i) 一般式（１）中のXは以下の群から選択され、かつ、Yは5α-cholest-8(14)-en3β-olである
パルミチン酸(16:0)、
ステアリン酸(18:0)、
2-ヒドロキシ-オクタデカン酸(18:0 (2h))、
オレイン酸(18:1)、
リノール酸(18:2)、又は、
リグノセリン酸(24:0)
(ii) 一般式（１）中のXは2-ヒドロキシ-オクタデカン酸(18:0 (2h))であり、かつ、Yは以下の群から選択される
Campesterol、
Stigmasterol、
5α-cholest-8(14)-en-3β-ol、又は、
β-Sitosterol

(i) X in the general formula (1) is selected from the following group, and Y is 5α-cholest-8 (14) -en3β-ol Palmitic acid (16: 0),
Stearic acid (18: 0),
2-hydroxy-octadecanoic acid (18: 0 (2h)),
Oleic acid (18: 1),
Linoleic acid (18: 2) or
Lignoceric acid (24: 0)
(ii) X in the general formula (1) is 2-hydroxy-octadecanoic acid (18: 0 (2h)), and Y is selected from the following group
Campesterol,
Stigmasterol,
5α-cholest-8 (14) -en-3β-ol, or
β-Sitosterol

[Evaluation using C57BL / 6j mice]
Focusing on the sterol glycoside fraction (ASG) contained in germinated brown rice, a high fat diet was administered to mice, and the effect on energy metabolism was examined.

<Example of preparation of ASG>
After removing the neutral lipid in the lipid component from the germinated brown rice bran with hexane, a crude extract of ASG was prepared for each residue using hexane, chloroform and methanol. This ASG crude extract was extracted with a chloroform: methanol (2: 1) mixture, and ASG was prepared by silica gel carrier column chromatography.
The extraction of ASG used in the test was performed using 200 kg of koji (koji accuracy 10%) obtained by scouring about 2,000 kg of germinated brown rice.
An amount of hexane soaked with rice bran (500 g) was added and stirred sufficiently, followed by filtration with gauze to obtain a defatted koji. Thereafter, the total fat fraction was extracted by adding chloroform: methanol 2: 1 (3 L) to 1.5 kg of defatted soot in which hexane was volatilized, and the extract was dried to dryness with an evaporator to obtain a dried product.

The dried product was dissolved in 300 ml of chloroform: hexane = 1: 1, and the whole solution was applied to a column of diameter 10 cm × length 100 cm (packed with 80 cm of Merck silica gel 60) swollen with chloroform. After all the solution had soaked into the iatrobeads, chloroform: hexane = 1: 1 (7,840 ml), chloroform (20,160 ml), chloroform: methanol = 9: 1 (10,080 ml) were passed in this order. Only a dark green solution separated by passing chloroform: methanol = 9: 1 was collected.
The collected dark green solution was dried to dryness using an evaporator. Table 1 shows the yield at each point.

[ASG analysis]
The extracted ASG was analyzed under the following conditions. As a result of this analysis, it was found that the final dried product contained 72.6% ASG.
Analysis conditions Detector: CoronaTM CADTM Charged Aerosol Detector
Column: LiChrospher Si 60 (5μm, 125 × 4mm id, Merck)
Column temperature: 40 degrees Flow rate: 1 mL / min.
Injection volume: 10μL
Sample solvent: chloroform: methanol (2: 1, vol / vol)
Calibration curve concentration: 10, 20, 40, 60 and 80 μg / mL
Mobile phase, gradient conditions (see Table 2)

[Animal testing / feed]
Seven-week-old male C57BL / 6j mice were used for the test. The test feed was prepared by adding 0.079% and 0.794% of ASG separated by the above-described method to a 30% fat diet, and adjusting the weight with β starch.
Table 3 shows the composition of the test feed.

[Dosing / Sample collection]
After grouping the high fat diet freely for 4 weeks to obtain an obesity model, the group is randomly divided into 3 groups (high fat diet group, low ASG diet group and high ASG diet group) so that there is no difference in the average body weight of each group Sorted out. The feed was powdered and each test feed was ingested freely for 66 days after grouping. The general condition was observed daily. Food intake was performed as much as possible so that the food consumption per week could be calculated. Body weight was measured every other week. Blood collection was performed with a heparin-Na-injected syringe under ether anesthesia after fasting for 4 hours the day after the administration was completed. The autopsy was performed after lethality by letting off the armpit arteries after blood collection, and the weight of the fat around the accessory testicles and kidneys was measured (Table 5). Breath analysis was performed on the end of administration. In addition, the amount of exercise is observed for 3 hours on the end of administration, and the amount of exercise indicates the total distance moved in centimeters (FIG. 2).

[Measurement]
For exhalation analysis, OXYMAX (Bio Research Center) was used to collect 24-hour exhalation gas and measure oxygen consumption (Fig. 1).
Table 4 shows the breath test and the visceral fat weight.
(Statistical analysis)
Each evaluation item was subjected to Tukey test as a multiple comparison test when there was a significant difference after one-way analysis of variance. The significance level between each group was P <0.05.

[Measurement result]
The oxygen consumption of the mice was higher in the ASG diet group than in the high fat diet group, confirming the enhancement of energy metabolism. In support of that, the testicular fat weight and perirenal fat weight reflecting visceral fat mass showed lower values in the ASG diet group compared to the high fat diet group.
In particular, as shown in FIG. 1, the oxygen consumption is higher in both the low ASG feed group and the high ASG group than in the high fat feed group, and the high concentration addition amount is larger. If the high fat feed group is 100%, the low ASG feed group is 109% and the high ASG group is 116%. In addition, as shown in FIG. 2, the amount of spontaneous exercise is increased in both the low ASG feed group and the high ASG group as compared with the high fat feed group, and the high concentration addition amount is larger. If the high fat feed group is 100%, the low ASG feed group is 153% and the high ASG group is 177%. Therefore, it can be seen that energy metabolism is enhanced in a concentration-dependent manner.
It was found that sterol glycosides in germinated brown rice improve the metabolic state by high fat diet and enhance energy metabolism.

The example of prescription using ASG of this invention is shown below.

Formulation Example 1
[Capsule]
Composition ASG ... 100mg
Beeswax 10mg
Grape seed oil… 110mg
The above ingredients were mixed and filled into a capsule base mixed with gelatin and glycerin to obtain soft capsules.

Formulation example 2
[tablet]
Composition ASG dried product ... 150mg
Cellulose ... 80mg
Starch ... 20mg
Sucrose fatty acid ester 2mg
The above components were mixed and tableted to obtain tablets.

Formulation Example 3
[Beverages]
(Composition) (Composition: Mass%)
Fructose butter sugar liquid sugar 5.00
Citric acid 10.4
L-ascorbic acid 0.20
Perfume 0.02
Dye 0.10
ASG dried product 1.00
Water 82.28

Claims (3)

  An energy metabolism enhancer comprising a sterol glycoside derived from germinated brown rice bran as an active ingredient.   A food or drink containing the energy metabolism enhancer according to claim 1 (excluding germinated brown rice). A pet food (excluding germinated brown rice) containing the energy metabolism enhancer according to claim 1.

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