JP2011148748A - Adiponectin secretion-promoting composition - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a safe and excellent adiponectin secretion-promoting composition capable of expecting the prevention or improving effect of arteriosclerosis, diabetic or metabolic syndrome by the elevation of adiponectin concentration in blood, and also without having adverse effects, and a preventing/improving agent, foodstuff, etc. of the arteriosclerosis, diabetic or metabolic syndrome by utilizing its secretion promoting effect. <P>SOLUTION: This adiponectin secretion-promoting agent containing porphyran as an active ingredient is provided, and the preventing and improving agent, foodstuff, etc. of the arteriosclerosis, diabetic or metabolic syndrome by utilizing the secretion-promoting effect are also developed. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

The present invention relates to a composition having an effect of preventing, improving or treating diabetes, metabolic syndrome, dyslipidemia or obesity, and a functional food or drink and feed containing them.
Specifically, adiponectin secretion promoting composition comprising porphyran derived from seaweed as an active ingredient, neutral fat reducing agent, anti-obesity agent, insulin resistance improving agent using the adiponectin secretion promoting composition, and performance thereof It is related with the functional food-drinks and feed which have.

  In recent years, an increase in lifestyle-related diseases such as diabetes, hypertension, and arteriosclerosis has been a problem, and excessive accumulation of visceral fat has been pointed out as one of the causes. It has been pointed out that when obesity due to visceral fat accumulation progresses, there is a high risk of multiple occurrences of the above symptoms such as diabetes, and arteriosclerosis progresses rapidly. Such a symptom is generally called a metabolic syndrome, and an immediate countermeasure is being demanded.

Adiponectin secreted from fat cells is a protein specifically produced and secreted from fat cells, and is known to be closely related to lifestyle diseases such as cardiovascular diseases, diabetes and obesity.
That is, it has become clear that adiponectin has a function of suppressing various cellular phenomena such as inflammation that causes arteriosclerosis in blood vessels.

As described above, adiponectin has also been confirmed to be associated with diabetes. When diabetic, the blood concentration of adiponectin decreases, and when the concentration of adiponectin increases, the blood glucose level decreases. This is presumed to be due to increased insulin sensitivity.
As the concentration of adiponectin is increased in this way, arteriosclerosis prevention, diabetes prevention / improvement effect or anti-obesity effect can be expected, and therefore, in recent years, a search for a substance that increases the production amount of adiponectin has been actively conducted.

  For example, Patent Document 1 discloses a composition comprising a fermented tea extract as an active ingredient as an adiponectin production enhancer. Patent Document 2 discloses an adiponectin secretion promoting composition containing green tea catechin as an active ingredient and increasing plasma adiponectin.

  Patent Document 3 discloses an adiponectin secretion promoting composition containing soybean saponin as an active ingredient. Patent Document 4 discloses an adiponectin secretion promoter containing sterol or a derivative thereof, which is an extract of rice bran, and is said to be able to promote secretion of more adiponectin from adipocytes. Furthermore, Patent Document 5 describes that an apple extract has an action of promoting an increase in the concentration of adiponectin in blood, and Patent Document 6 describes that a turmeric rhizome extract has a similar effect. Yes.

  As described above, it has been clarified that adiponectin plays an important role in the pathology of diabetes and metabolic syndrome, but the above-mentioned various extracts are known as those that increase adiponectin in blood. Although they have been proposed, they have a complicated extraction method and have a problem in flavor when added to foods, and they still do not have sufficient performance.

On the other hand, porphyran is a high molecular acidic polysaccharide containing a sulfate group extracted from algal bodies of the red alga Amori (Susabinori, Asakusanori, Malva amanori, etc.), which has been popular in Japan for many years as a dry plate seaweed or boiled in seaweed. This porphyran is composed of D-galactose, 3,6-anhydro-L-galactose, 6-O-methyl-D-galactose, L-galactose-6-
It contains sulfuric acid and is structurally similar to agar, but is rich in L-galactose-6-sulfuric acid and does not show gelling ability like agar.

  In recent years, detailed structural analysis has progressed by instrumental analysis using NMR, etc., and porphyran has agarose agarobiose as a basic unit, one of which is sulfated by 2 to 2.5 units. It has been reported that it contains about 6-11% sulfate groups.

  In addition, porphyran, like other sulfated polysaccharides, is capable of adsorbing metal ([Non-Patent Document 1]), improving intestinal flora ([Non-Patent Document 2]), antitumor activity ([Non-Patent Document 3], [Non-patent document 4]), having a physiological activity such as immunostimulatory action ([non-patent document 5], [non-patent document 6], [non-patent document 7]), and being usable as an active ingredient of an obesity inhibitor ( [Patent Document 7]) has been reported, but no report has been made on the fact that porphyran has an adiponectin secretion promoting effect.

JP 2004-315379 A JP 2006-131512 A JP 2006-143609 A JP 2005-68132 A JP 2006-193502 A JP 2005-60308 A JP-A-62-428

Genji Ishibashi “Changes in physicochemical properties of Asakusanori porphyran by heating operation” Bulletin of Kyushu Women's University 1990, 26, 15-21) Daisuke Kawazu et al. “Effects of Susabinori polysaccharides on intestinal flora”, Nissui 1995, 61, 59-69) Noda et al. "Studies on the antitumor activity of marine algae" Nippon Suisan Gakkaishi 1989, 55, 1259-1264 Noda et al. “Antitumour activity of polysaccharides and lipids from marine algae”, Nippon Suisan Gakkaishi 1989, 55, 1265-1271) Yoshizawa et al. "Activation of marine macrophages by polysaccharide fractions from marine algae (Porphyra yezoensis)" BBB. 1993, 57, 1862-1866 Yasuko Yoshizawa et al. “Research on immunostimulatory polysaccharides derived from red algae” Food Industry 1994, 37, 25-30 Yoshizawa et al., “Macrophage stimulation activity of the polysaccharide fraction from a marine Algae (Porphyra yezoensis): Structure-function relationships and improved solubility” B.B.B. 1995, 59, 1933-1937)

An object of the present invention is to provide a safe and excellent adiponectin secretion-promoting composition that can be expected to prevent or ameliorate arteriosclerosis or diabetes and metabolic syndrome by increasing the concentration of adiponectin in the blood, and its The purpose is to provide an arteriosclerosis, diabetes or metabolic syndrome prevention, ameliorating agent, food and the like using a secretory promoting action.
That is, an object of the present invention is to provide a composition that can promote secretion of adiponectin and to develop pharmaceutical preparations, foods, and feeds that are useful for treatment and prevention of various diseases based on the composition for promoting secretion of adiponectin.

As a result of intensive studies to solve the above problems, the present inventors have found that porphyran or a salt thereof has an adiponectin secretion promoting effect, and have completed the present invention.
That is, (1) The present invention provides an adiponectin secretion promoting composition comprising porphyran or a salt thereof as an active ingredient.
Moreover, (2) this invention provides the adiponectin secretion promotion composition as described in (1) which contains porphyran or its salts with a powder, granule, or liquid.

Moreover, (3) this invention provides the adiponectin secretion promotion composition as described in (1) or (2) containing the porphyran extracted from the 1 or several genus Amanori selected from the group containing a clam and a sausobiori. .
Moreover, (4) this invention provides the adiponectin secretion promotion composition in any one of (1)-(3) which is a neutral fat reducing agent.
Moreover, (5) this invention provides the adiponectin secretion promotion composition in any one of (1)-(3) which is an antiobesity agent.

Moreover, (6) this invention provides the adiponectin secretion promotion composition in any one of (1)-(3) which is an insulin resistance improving agent.
Moreover, (7) this invention provides the adiponectin secretion promotion composition in any one of (1)-(3) which is a food-drinks additive.
Moreover, (8) this invention provides the functional food-drinks food / beverage products which have the adiponectin secretion promotion effect containing the adiponectin secretion promotion composition in any one of (1)-(3).

Moreover, (9) this invention provides the functional food / beverage products as described in (8) for neutral fat reduction.
Moreover, (10) this invention provides the functional food / beverage products as described in (8) for obesity improvement.
(11) The present invention provides the functional food or drink according to (8) for improving insulin resistance.
Moreover, (12) this invention is a film form, The functional food / beverage products in any one of (8)-(11) characterized by the above-mentioned are provided.

Moreover, (13) this invention provides the feed which has the adiponectin secretion promotion effect containing the adiponectin secretion promotion composition in any one of (1)-(3).
Moreover, (14) this invention provides the feed as described in (13) which has an insulin resistance improvement effect.

  Since the composition of the present invention has a high adiponectin secretion-promoting effect, it can provide pharmaceutical preparations, foods and drinks, and feeds using the same. Improvement of insulin resistance, metabolic syndrome, diabetes It is useful for the treatment and prevention of infectious diseases, etc., and is also expected to reduce triglycerides and prevent obesity.

2 is a graph showing plasma adiponectin concentration and insulin concentration in a control group and a porphyran intake group in Example 1. FIG. 2 is a graph showing plasma glucose concentrations in a control group and a porphyran intake group in Example 1. FIG. 2 is a graph showing plasma triacylglycerol concentration and total cholesterol concentration in a control group and a porphyran intake group in Example 1. FIG. 2 is a graph showing body weights in a control group and a porphyran intake group in Example 1. FIG. It is a graph which shows the tissue weight (liver) in the control group in Example 1, and a porphyran intake group. It is a graph which shows the tissue weight (kidney) in the control group and porphyran intake group in Example 1. It is a graph which shows the tissue weight (spleen) in the control group and porphyran intake group in Example 1. 2 is a graph showing the total weight of adipose tissue (epididymis, perirenal, mesentery) in the control group and porphyran intake group in Example 1.

Hereinafter, the present invention will be described in more detail including examples.
The raw material for extracting porphyran or a salt thereof used in the present invention is not particularly limited. In addition, from the viewpoint of supply stability, it is preferable to use the above-mentioned Asakusa Nori or Susabi Nori for the extraction material. Moreover, they can be in any form such as fresh seaweed, dried seaweed, and grilled seaweed.

Reference Example 1 Production Example of Porphyran or Salts thereof Extraction was performed at 95 ° C. for 3 hours with 12 kg of purified water obtained by boiling 1 kg of dried seaweed from Kyushu Ariake Sea. Next, the extraction residue is filtered with a 50 mesh shifter, diatomaceous earth corresponding to 1% and activated carbon corresponding to 5% are added to the extract, and centrifugation (14000 rpm, 10 minutes) is performed to obtain an extraction residue. The coloring substance and odor were completely removed to obtain an extract.
Then, (1) Concentrate the extract, add ethanol to a final concentration of 80%, leave it in ethanol for 24 hours, precipitate porphyran, and dry the resulting precipitate to obtain a powder. Alternatively, the extract was concentrated and spray-dried to obtain a powder. (P group)

Or (2) The extract is passed through a cation exchange resin or an anion exchange resin, then neutralized with arginine (PA group, arginine salt), or after anion exchange, neutralized with KOH (PK group, potassium) Salt) purification step was performed to obtain a purified extract. Then, the purified extract is concentrated, ethanol is added to a final concentration of 80%, and the porphyran is precipitated after standing in ethanol for 24 hours, and the resulting precipitate is air-dried to obtain a powder, Alternatively, the purified extract was concentrated and spray-dried to obtain a powder.
Further, porphyran salts were prepared in the same manner as calcium salts and sodium salts.

Porphyran or a salt thereof used in the adiponectin secretion-promoting composition of the present invention may be in the form of powder, granules, film, or liquid, and may contain impurities if the amount is small, but the degree of purification is at least 50% or more. , Preferably 70% or more, more preferably 85% or more.
In addition, the porphyran of this invention can use what contains other sulfated polysaccharides, such as a fucoidan, besides porphyran.
In addition, the adiponectin secretion promoting composition of the present invention can be used as a pharmaceutical preparation together with a carrier, and can be ingested by being mixed with various foods and drinks, feeds (pet foods, etc.).

When the adiponectin secretion-promoting composition of the present invention is used as a pharmaceutical preparation, it is suitably used as an insulin resistance improving agent, a preventive or therapeutic agent for metabolic syndrome, a preventive or therapeutic agent for diabetes and its complications, and a neutral fat reducing agent. .
The pharmaceutical preparation is appropriately used orally or parenterally. The dosage form is also arbitrary, for example, oral solid preparations such as tablets, granules, powders and capsules, oral liquid preparations such as internal liquids and syrups, and parenteral liquid preparations such as injections. These forms can also be appropriately prepared by known methods.

These pharmaceutical preparations include commonly used excipients such as saccharides and starches, binders such as crystalline cellulose and pullulan, disintegrants such as carboxymethylcellulose, and other agents, thickeners, dispersants, buffers, and dissolution agents. Adjuvants, preservatives, pH adjusters and the like may be used as appropriate.
In the case of a solid preparation, it is preferable that porphyran is contained in the preparation in an amount of 30 to 90% by weight in consideration of ease of preparation. In the case of a liquid preparation, it is easy to take. , Preferably 0.1 to 5% by weight.

In the pharmaceutical preparation of the present invention, the dose (actual amount) of porphyran or its salt, which is an active ingredient, varies depending on the dosage form, the patient's body weight, indication symptoms, etc. It is preferably administered once to several times, and is administered in an amount of about 0.01 to 60 g, preferably about 0.1 to 50 g per day.
When the adiponectin secretion-promoting composition of the present invention is used as a food or drink, feed, etc., in addition to general food and drink, the insulin resistance is improved, the prevention and treatment of metabolic syndrome, and the prevention and treatment of diabetes and its complications. It can be applied to functional foods and beverages displaying specific functions, foods for specific insurance, and the like.

As a form of food / beverage products, it can shape | mold arbitrarily, for example in the shape of a granule, a granular form, a paste form, solid form, or a liquid. These include various known substances that are recognized to be contained in foods, such as binders, thickeners, dispersants, corrigents, buffers, solubilizers, preservatives, emulsifiers and pH adjusters. Etc. can be appropriately contained.
The content of porphyran or its salts, which is an active ingredient contained in the food or drink of the present invention, can be appropriately determined according to the purpose, form, usage method, and the like. For example, in the case of solid food, the content can be about 5 to 90% by weight, preferably about 30 to 80% by weight, and in the case of liquid food, about 0.1 to 10% by weight, preferably 3 to 3% by weight. The content can be about 5% by weight.
In particular, when used as a health food or drink, it is preferable to contain the active ingredient of the present invention in such an amount that a predetermined effect is sufficiently exhibited.
The content of porphyran, which is an active ingredient contained in the feed of the present invention, or a salt thereof is also about the same as in the case of the above food and drink.

EXAMPLES Hereinafter, although this invention is demonstrated further in detail based on an Example, this invention is not limited to a following example.
Example 1
Using 24 KK-Ay mice (male, 4 weeks old), a model of obesity type 2 diabetes, the control group (Group C) so that the average body weight between the groups was almost equal after one week of preliminary breeding. 6) and 3 groups of porphyran intake produced in Reference Example 1, ie, porphyran free salt intake group (P group, 6 animals), porphyran arginine salt intake group (PA group, 6 animals), porphyran potassium salt intake Each group was divided into a total of 4 groups (PK group, 6 animals).

In the control group, AIN-93G was used as a basic composition, and a high fat diet containing 14% soybean oil (7% of β-corn starch was replaced with soybean oil and approximately 30% as energy) was freely consumed and drunk.
Each porphyran intake group (P group, PA group, PK group) was allowed to freely ingest and drink a porphyran-added high fat diet in which cellulose (containing 5%) contained in the high fat diet was replaced with each porphyran sample. .

The composition of AIN-93G is as follows.
Formulation (%)
Casein 20.0
L-cystine 0.3
β-corn starch 39.7486
α-Corn Starch 13.2
Sucrose 10.0
Soybean oil 7.0
Cellulose powder 5.0
AIN-93G mineral mixing 3.5
AIN-93G vitamin mix 1.0
Choline bitartrate 0.25
Tertiary butyl hydroquinone 0.0014
Total 100.0

Each of the above feeds was allowed to be ingested and drunk for 3 weeks for each group, and a breeding test was conducted. During the breeding test, food consumption (daily) and body weight (three times a week) were measured. After the test period, the organs were removed after fasting for 12 hours and collecting blood under isoflurane anesthesia.
From the results of measurement of food intake (daily) and body weight (3 times a week) during the breeding test, no abnormal phenomenon was observed in each group due to changes in food intake and body weight during the breeding test.
After dissection, the following items were measured.
<Organ weight> Total of liver, kidney, spleen, and adipose tissue (epididymis, perirenal, mesentery)
<Plasma component> Triacylglycerol (TG), total cholesterol (T-Cho), glucose, insulin, adiponectin

The plasma adiponectin concentration was measured using an adiponectin measurement ELISA kit (manufactured by Quantikine R & D systems, Inc.), and the plasma insulin concentration was measured using an insulin measurement ELISA kit (manufactured by PHOENIX PHARMACEUTICALS. INC.). Measured. About other than that, it analyzed by the conventional method.
The measurement result of the adiponectin concentration is shown in FIG. As is clear from the results of FIG. 1, the plasma adiponectin concentration was significantly increased (P <0.05) in the porphyran intake group as compared to the control group.

Moreover, as for the insulin concentration in plasma, as shown in FIG. 1, the fall of the insulin concentration in plasma was seen by ingesting porphyran.
As described above, in the porphyran intake group, the plasma adiponectin concentration increased and at the same time the plasma insulin concentration decreased, and the blood glucose level also decreased as shown in FIG. This is clearly shown by the experimental results.
Further, the triacylglycerol concentration and the total cholesterol concentration in plasma also show a clear tendency to decrease by ingesting porphyran as shown in FIG.

As described above, porphyran is an excellent prophylaxis against various diseases caused by decreased plasma concentrations of adiponectin, increased insulin resistance, etc., such as metabolic syndrome, diabetes and its complications. It was confirmed to have a therapeutic effect.
Moreover, as seen in FIGS. 4 to 7, the body weight and the weights of the liver, kidney and spleen are also found to decrease in the porphyran intake group compared to the control group.
Further, FIG. 8 shows that the total weight of adipose tissue (epididymis, perirenal, and mesentery) also shows a tendency to decrease in the porphyran intake group compared to the control group. It was confirmed that it has the effect of reducing fat and anti-obesity.

Furthermore, the same effect was confirmed when calcium salt and sodium salt were used as porphyran.
Moreover, the same effect was confirmed also when porphyran contains fucoidan.
Next, the functional food / beverage products and feed containing the adiponectin secretion promoting composition containing the porphyran or salts thereof of the present invention will be specifically described.

(1) Example of functional beverage formulation having adiponectin secretion promoting action Porphyran 50 g
Apple concentrate 50g
150g sugar
Citric acid 1g
Perfume proper amount water 750g

(2) Sticky functional food formulation example having adiponectin secretion promoting action Porphyran 3000mg
Granulated sugar 900mg
Dextrin 6000mg
Perfume

(3) Feed formulation example having adiponectin secretion promoting action Porphyran 5g
Nonfat dry milk 57g
7g soybean meal
7g palm oil
Corn starch 10g
10g sugar
1g of vitamin mixture
3g of mineral mixture
Functional foods and feeds having an adiponectin secretion-promoting action containing porphyran or salts thereof having the above composition could be used in the same manner as ordinary foods and feeds.

Since the composition containing porphyran or a salt thereof of the present invention has a high secretion promoting effect of adiponectin, it is possible to provide pharmaceutical preparations, foods and drinks, and feeds using the same, and to improve various insulin resistances involving adiponectin The improvement of plasma adiponectin concentration is useful for the treatment and prevention of various pathologies such as metabolic syndrome, diabetes and its complications, and is also expected to reduce triglycerides and prevent obesity.

Claims (14)

  An adiponectin secretion promoting composition comprising porphyran or a salt thereof as an active ingredient. 2. The adiponectin secretion promoting composition according to claim 1, comprising the porphyran or a salt thereof in a powder or liquid form.   The adiponectin secretion-promoting composition according to claim 1 or 2, wherein the porphyran is extracted from one or more genus Amano selected from the group comprising Asakusanori and Susabiori.   The composition for promoting adiponectin secretion according to any one of claims 1 to 3, wherein the composition is a neutral fat reducing agent.   The composition for promoting adiponectin secretion according to any one of claims 1 to 3, wherein the composition is an anti-obesity agent.   The adiponectin secretion promoting composition according to any one of claims 1 to 3, wherein the composition is an insulin resistance improving agent.   The composition for promoting adiponectin secretion according to any one of claims 1 to 3, wherein the composition is a food or drink additive.   A functional food or drink having an adiponectin secretion promoting action, comprising the adiponectin secretion promoting composition according to claim 1.   The functional food or drink according to claim 8, which is used for reducing neutral fat.   The functional food or drink according to claim 8, which is used for improving obesity.   The functional food or drink according to claim 8, which is for improving insulin resistance.   It is a film shape, The functional food-drinks in any one of Claims 8-11 characterized by the above-mentioned.   A feed having an adiponectin secretion promoting action, comprising the adiponectin secretion promoting composition according to any one of claims 1 to 3.   The feed according to claim 13, which has an insulin resistance improving action.

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