JP2006347978A - Anti-obesity agent, and food and pet food containing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an adiposity inhibitor and anti-obesity agent, both of which can be daily and confidently taken in; a foodstuff additive containing the adiposity inhibitor; and a foodstuff and a pet food prepared by compounding them. <P>SOLUTION: Each of the adiposity inhibitor, the anti-obesity agent, the food additive, and the food and pet food contains lignans as effective components. An especially most suitable lignan is secoisolariciresinol diglycoside, and in addition, lignans of matairesinol, pinoresinol, isolariciresinol, etc., are also contained. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a fat accumulation inhibitor containing lignan as an active ingredient, an anti-obesity agent, a food additive containing the fat accumulation inhibitor, and a food and pet food containing these.

Lignans are known as anticancer substances and antioxidant substances (see, for example, Patent Document 1).
It is also known as phytoestrogen.
Linseed contains a large amount of the lignan.
In particular, secoisolaricillinol diglycoside (hereinafter also referred to as SDG) is contained in the largest amount, and lignans such as matalesinol, pinoresinol, isolaresirinol are also contained in a small amount.
Other than flaxseed, it is easily contained in plants with high fiber content, and in grains, it is contained in wheat beans, barley, buckwheat, and beans in kidney beans and soybeans (for example, see Non-Patent Document 1).

JP-A-9-208461 Diane H. Maurice, “Amani Booklet on Health and Nutrition”, 1st edition, 1994, p. 1-78

In recent years, it has been elucidated that obesity is linked to diabetes, hyperlipidemia and hypertension, resulting in arteriosclerotic diseases such as ischemic heart disease and stroke.
In addition, obesity is caused by the accumulation of excess fat in adipocytes in adipose tissue, but it is thought that the current high-calorie, high-fat diet is the cause.
An object of the present invention is to provide a fat accumulation inhibitor, an anti-obesity agent, a food additive containing the fat accumulation inhibitor, and a food and a pet food containing the same, which can be taken with peace of mind on a daily basis.

（式中、Ｒ１〜Ｒ４はそれぞれ独立して水素原子または炭素数１〜３のアルキル基、Ｒ５、Ｒ６はそれぞれ独立してヒドロキシル基、あるいはグルコース、ガラクトースおよびフルクトースからなる群から選ばれる１種また２種以上の糖が１〜３個グリコシド結合した糖鎖残基、あるいはＲ５、Ｒ６が一緒になって酸素原子を表す。）
（２）前記化学式（１）で示されるリグナンを有効成分として含有することを特徴とする抗肥満剤である。
（３）前記脂肪蓄積抑制剤を含有することを特徴とする食品添加物である。
（４）前記脂肪蓄積抑制剤又は前記食品添加物を配合したことを特徴とする食品である。
（５）前記脂肪蓄積抑制剤を含有することを特徴とするペットフードである。 As a result of intensive studies to achieve the above-mentioned object, the present inventor has found that lignans contained in a large amount in flaxseed seeds have a fat accumulation-inhibiting action and have completed the present invention.
Therefore, the present invention
(1) Fat accumulation suppression characterized by containing a lignan represented by the following chemical formula (1) as an active ingredient.

(Wherein R1 to R4 are each independently a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, R5 and R6 are each independently a hydroxyl group, or one kind selected from the group consisting of glucose, galactose and fructose; (A sugar chain residue in which two or more kinds of sugars are linked by 1 to 3 glycosides, or R5 and R6 together represent an oxygen atom.)
(2) An anti-obesity agent comprising a lignan represented by the chemical formula (1) as an active ingredient.
(3) A food additive comprising the fat accumulation inhibitor.
(4) A food comprising the fat accumulation inhibitor or the food additive.
(5) A pet food comprising the fat accumulation inhibitor.

  Even when eating a high-calorie and high-fat meal with the anti-obesity agent of the present invention, accumulation of body fat can be suppressed and obesity can be prevented.

Hereinafter, the present invention will be described in detail.
The lignan used in the present invention is represented by the chemical formula (1).
In the formula, R1 to R4 are each independently a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, R5 and R6 are each independently a hydroxyl group, or one or two kinds selected from the group consisting of glucose, galactose and fructose A sugar chain residue in which 1 to 3 sugars of one or more species are glycosidic bonded, or R5 and R6 together represent an oxygen atom.

（式中、Glcはグルコース残基を表す） Linseed contains the most abundant secoisolarisiresinol diglycoside (SDG) represented by the following chemical formula (2).

(In the formula, Glc represents a glucose residue)

Glycosides other than SDG in the present invention can be easily produced by a method using a known glycosyltransferase using SDG as a raw material.
In addition, the substituents represented by R5 and R6 in the above formula are considered to hardly affect the physiological activity because they are separated in vivo.

SDG can be obtained by chemical synthesis, or can be obtained by extraction and purification from flax seeds by a known method.
For example, flaxseed is pulverized by a pulverizer such as a mixer or a homogenizer. The flaxseed to be used can be used regardless of whether it is roasted or non-roasted, regardless of whether it is a domestic or foreign production region, or a variety for cultivation or oil extraction. Alternatively, flaxseed meal produced in the oil extraction process may be used as a raw material. The pulverized product may be degreased by removing oil with a fat-soluble organic solvent such as n-hexane. Extract with lower alcohol (ethanol, methanol, n-propanol, isopropanol, n-butanol, etc.) that can extract SDG, or its hydrous alcohol, saponify and neutralize if necessary, octadecyl silica as adsorbent (ODS), silica gel and the like can be used for fractionation and purification.

A product obtained by concentrating and drying the SDG purified fraction is a brownish brown powder and is dissolved in water, hydrous alcohol or the like.
Since the storage is an antioxidant, it is preferable to store in a cool and dark place.
Since it is stable against heat and pH, it can be incorporated into fat accumulation inhibitors, anti-obesity agents, food additives, foods and pet foods.

  As a fat accumulation inhibitor and an anti-obesity agent, a fat accumulation inhibitor and an anti-obesity agent that can be administered orally or parenterally can be formulated into an arbitrary form together with an auxiliary agent by a known method.

When administered orally, it can be administered as capsules or tablets, granules, fine granules, powders, and the like.
When administered parenterally, it can be administered in dosage forms such as injections, drops, and suppositories, administered locally, intradermal, subcutaneous, intramuscular and intravenous injection, topical application, spray, suppository Also, an external administration method such as intravesical injection can be used.

  The dose may vary depending on the administration method and the patient's age, medical condition, general condition, etc., but usually 10 to 60,000 mg as an active ingredient per day is appropriate for adults and 10 to 30,000 mg for small children. Is appropriate.

The fat accumulation inhibitor of the present invention can be incorporated into general foods and health foods, and can also be used as a component of food additives.
The food containing the fat accumulation inhibitor or food additive of the present invention is not particularly limited, and examples thereof include bakery foods such as bread, confectionery bread, pies, Danish, donuts, cakes, udon, soba, Chinese noodles, yakisoba, pasta, etc. Examples include noodles, fried foods such as tempura and croquettes, sauces such as curry, stew and dressing, sprinkles, kneaded products such as kamaboko, beverages such as juice, snacks, rice cakes, rice cakes, confectionery such as gum .

The fat accumulation inhibitor of the present invention can also be added to pet food.
Pet food refers to food for mammal pets 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.

Hereinafter, the present invention will be specifically described by way of examples.
[Extraction purification]
Linseed seeds were pulverized, degreased with n-hexane, and then subjected to reflux extraction with hydrous methanol.
The extract was saponified and neutralized, and then the SDG fraction was purified using okdadecyl silica and silica gel as adsorbents.

The SDG content was confirmed by high performance liquid chromatography, and the molecular weight was confirmed by a time-of-flight mass spectrometer (hereinafter also referred to as TOF / MS).
The measurement result by high performance liquid chromatography is shown in FIG. 1, and the measurement result of molecular weight by TOF / MS is shown in FIG.
The highest peak in FIGS. 1 and 2 is SDG.

[Safety test]
(1) Acute toxicity test As part of the safety study of a 20% SDG content product (60% SDG product: Diluent α-cyclodextrin, 1: 2 mixed), mice (female, male) are used as a single oral dose. Acute toxicity test by administration was conducted. The dosage was 2.5 g / kg, 1.25 g / kg, and 0.625 g / kg, with 5 g / kg as the maximum.

As a result, no death was observed in any group, and no abnormalities were observed as general symptoms during the observation period. Furthermore, in the pathological anatomy, none of the groups showed any abnormality.
From the above results, the acute toxicity value (LD50 value) for SDG 20 mass% mice (male and female) was 5 g / kg or more, indicating that this substance is a very safe substance.

(2) Mutagenicity test The mutagenicity of 20 mass% SDG product was tested using Saomonella typhimurium TA100, TA1535, TA98, TA1537 and Escherichia coli WP2uvrA strain. As a result, no gene mutation was induced in any of the strains used in the direct method and metabolic activation method in 20% by mass of SDG.

[Example 1]
[Confirmation of preadipocyte differentiation inhibitory effect]
In fat cells, activities such as glycerol-3-phosphate dehydrogenase (GPDH), an enzyme involved in the synthesis and degradation of neutral fat, are remarkably increased, and oil droplets of neutral fat accumulate in the cells.
Using this principle, the effect of flaxseed SDG on fat accumulation was examined using mouse preadipocytes.
Preadipocytes (3T3-L1) are cultured at 37 ° C., reach confluence, and then cultured in a medium containing insulin, dexamethasone, and isobutyl-1-methylxanthine to differentiate into adipocytes. The size of the neutral fat particles after differentiation was observed over time. In observing the extent of fat accumulation, flaxseed SDG was added simultaneously with insulin, dexamethasone, and isobutyl-1-methylxanthine.
The degree of differentiation was determined by measuring the activity of glucerol-3-phosphate dehydrogenase (hereinafter also referred to as GPDH), which is a differentiation marker. The GPDH activity was measured 4 times and expressed as an average value ± standard deviation.
Using refined flaxseed SDG content 88% powder, it was added to the medium to 0.5 mg / ml and 1.0 mg / ml.
The statistical test was analyzed by Fischer's least significant difference method after ANOVA analysis.
The other tests were similarly statistically processed.

濃度依存的なＧＰＤＨ活性の低下が確認され、脂肪蓄積の抑制傾向があることからアマニＳＤＧの肥満予防効果が確認できた。 The results are shown in Table 1.

The concentration-dependent decrease in GPDH activity was confirmed and the tendency to suppress fat accumulation was confirmed, and the effect of flaxseed SDG on preventing obesity could be confirmed.

[Body weight suppression test]
Seven-week-old male C57BL / 6 mice (obtained from Japan SLC Co., Ltd.) were used as experimental animals.
The mice were fed with a normal diet for 1 week, and then divided into 3 groups (5 animals / group). The diet shown in Table 2 was freely fed for 8 weeks and the change in body weight was measured.
Water was given tap water freely.
The feed was divided into light-shielding bags every two days and stored at 4 ° C.

アマニＳＤＧを加えることで体重増加抑制効果が確認された。 Table 3 shows the measurement results of changes in the body weight of the mice.

By adding flaxseed SDG, an effect of suppressing weight gain was confirmed.

[Fat weight suppression test]
After 8 weeks, the mice were fasted for 18 hours and anesthetized with ether, and immediately laparotomized to collect visceral fat (perirenal fat and peripheral fat of the testicle) and weighed.

高脂肪食群と有意に差がある群；^*P<0.05
高脂肪食摂取群と比較して、高脂肪食に1.0％ＳＤＧ添加群で腎周囲脂肪は有意に減少し、副睾丸周囲脂肪は減少傾向が認められた。 Table 4 shows the weight measurement results.

Group significantly different from high fat diet group; ^* P <0.05
Compared to the high fat diet intake group, the perirenal fat was significantly decreased and the epididymal fat decreased in the 1.0% SDG addition group to the high fat diet.

[Example 2]
(Manufacture of tablet confectionery and tablets)
Egg shell calcium (108 g), ferric pyrophosphate (2 g), ascorbic acid (40 g), microcrystalline cellulose (40 g), reduced maltose (280 g) and SDG (25 g) were mixed by a conventional method using a mixer and then tableted to produce tablet confections and tablets.

[Example 3]
(Manufacture of biscuits)
120g of wheat flour, 2g of SDG, 35g of sugar, 15g of shortening, 2g of whole egg powder, 1g of sodium chloride, 0.6g of sodium bicarbonate, 0.75g of ammonia carbonate, 20g of water Biscuits were manufactured.

[Example 4]
(Manufacture of bread)
Using 3kg flour, 3g SDG, 60g yeast, 3g yeast food, 150g sugar, 60g salt, 150g shortening, 60g nonfat dry milk, 2.1kg water, make dough by conventional methods, mold and bake to produce bread did.

[Example 5]
(Manufacture of udon)
After adding 1 part by weight of SDG, 40 parts by weight of water and 3 parts by weight of salt to 100 parts by weight of medium-strength flour, the mixture is kneaded by a conventional method, combined once and rolled three times, then cut. Cut out with blade No. 10 to obtain noodle strings of udon.
The udon was boiled for 13 minutes to obtain udon.

[Example 6]
(Manufacture of pet food)
Frozen beef 75 parts by mass, fats and oils 2 parts by mass, wheat protein 10 parts by mass, propylene glycol 5 parts by mass, flour 8 parts by mass, and SDG 1 part by mass were kneaded and dried by a conventional method to obtain a rod-shaped dock food.

[Example 7]
(Manufacturing supplements)
Tablets are made using 35 parts by weight of maltitol, 20 parts by weight of dextrin, 10 parts by weight of eggshell calcium, 10 parts by weight of dietary fiber, 5 parts by weight of vitamin mix, 5 parts by weight of sucrose fatty acid ester, and 15 parts by weight of SDG. I got a supplement.

It is a measurement result of SDG content by high performance liquid chromatography. It is a measurement result of SDG molecular weight by a time-of-flight mass spectrometer (TOF / MS).

Claims (5)

A fat accumulation inhibitor comprising a lignan represented by the following chemical formula (1) as an active ingredient.

(Wherein R1 to R4 are each independently a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, R5 and R6 are each independently a hydroxyl group, or one kind selected from the group consisting of glucose, galactose and fructose; (A sugar chain residue in which two or more kinds of sugars are linked by 1 to 3 glycosides, or R5 and R6 together represent an oxygen atom.)   An anti-obesity agent comprising the lignan according to claim 1 as an active ingredient.   A food additive comprising the fat accumulation inhibitor according to claim 1.   A food comprising the fat accumulation inhibitor according to claim 1 or the food additive according to claim 3. A pet food comprising the fat accumulation inhibitor according to claim 1.

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